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Race is an important determinant of folate status

by hitssquad
Tags: determinant, folate, important, race, status
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hitssquad
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Aug20-04, 04:00 AM
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J Nutr. 2004 Jul;134(7):1786-92.

Ethnicity and race influence the folate status response to controlled folate intakes in young women.

Perry CA, Renna SA, Khitun E, Ortiz M, Moriarty DJ, Caudill MA.


Department of Human Nutrition and Food Science, Cal Poly Pomona University, Pomona, CA 91768, USA.

Population-based studies report differences in folate status indicators among Mexican American (MA), African American (AA) and Caucasian (CA) women. It is unclear, however, whether these differences are due to variations in dietary folate intake. The present study was designed to investigate the influence of ethnicity/race on folate status parameters in MA, AA, and CA women (18-45 y; n = 14 in each group) under conditions of strictly controlled folate intake. In addition, the adequacy of the 1998 folate U.S. recommended dietary allowance (RDA), 400 micro g/d as dietary folate equivalents (DFE), for non-Caucasian women was assessed. Subjects (n = 42) with the methylenetetrahydrofolate reductase 677 CC genotype consumed a low-folate diet (135 micro g DFE/d) for 7 wk followed by repletion with 400 (7 MA, 7 AA, 7 CA) or 800 micro g DFE/d (7 MA, 7 AA, 7 CA) for 7 wk. AA women had lower (P </= 0.05) blood folate concentrations and excreted less (P </= 0.05) urinary folate throughout folate depletion and repletion with 400 and/or 800 micro g DFE/d compared with MA and/or CA women. MA women had lower (P </= 0.05) plasma total homocysteine (tHcy) throughout folate depletion and during repletion with 400 micro g DFE/d relative to the other ethnic/racial groups. Repletion with the 1998 folate U.S. RDA led to normal blood folate and plasma tHcy for all 3 ethnic/racial groups. Collectively, these data demonstrate that ethnicity/race is an important determinant of folate status under conditions of strictly controlled dietary folate intake and support the adequacy of the 1998 folate U.S. RDA for the 3 largest ethnic/racial groups in the United States.

PMID: 15226470
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Monique
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Aug20-04, 07:15 AM
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You missed the catch phrase
It is unclear, however, whether these differences are due to variations in dietary folate intake.
edit: never mind, the phrase is part of the introduction and not the study.
marcus
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Aug20-04, 08:52 AM
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Quote Quote by Monique
You missed the catch phrase
Hi Monique, I am curious as to why you think hits "missed the catch phrase".
what you refer to is the second sentence of the abstract! How could anyone miss it?

If I had gone to the trouble hits did, to find this article and post it and the abstract, I would be disappointed if someone reacts like that and tells me that I didnt read the second sentence of what I posted!

Nereid is always posting these quotes from authority which indicate that
some scientists find the concept of human race useful in their work----why should hits not also want to do this?

Please let us not impute questionable motives to each other especially in an unthinking way! Maybe you believe that hits is a bad person, or stupid, from some other posts. But i do not know anything about this and I see that this post is not bad or stupid.

It just makes the same point as we see in many large quotes from Cavalli-S that Nereid brings us-----some scientists use the term race in their work.

Indeed in Nereid's quotes it says that some use 3 race categories for humans and some use 60 categories. The diversity in usage suggests that different researchers have different applications. In hits article there are 3 categories and it is a specifically US situation. Also the article leave it an open question whether or not there is any genetic link----it could be, or on the other hand, it might not be.

If you are a dietician and young woman comes into your office for consultation and you notice that they are some "race/ethnicity" type (I forget which but the article will say) then it is a signal to you to make extra sure that the young woman is getting enough folate uptake.

The article seems like OK science---the use of category seems unemotional----there is no ax to grind (no Monoracist or Master-race ideology being pushed).

So is there anything wrong either with the article or with hitssquad?
Any reason for a defensive response?

I know from other contexts that you are flexible and un-ideological in your thinking, and an extremely nice person, so I am curious.
Or were you just kidding hitssquad, when you say he or she missed reading the second sentence of the inpasted abstract?

Monique
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Aug20-04, 10:05 AM
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Race is an important determinant of folate status

You jump to quick conclusions about me marcus, you could have just told me I missed the conclusion. I think the authors should have stated that "It was unclear, however, whether these differences are due to variations in dietary folate intake."

I'd like to see the article in print since I am interested in what kind of statistics they did, what the spread of the datapoints is within and between the ethnic groups (since they only have 7 datapoint per group), and how they sampled their participants. To be clear: I have nothing against articles like these, I'm just curious how they handled the issues.
iansmith
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Aug20-04, 10:21 AM
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Monique, the phrase that you pointed out states the problem not the conclusion. The placement of sentences in abstract is the key to determine its purpose.

This is the purpose of the study from the introduction of the article.

The purpose of this study was to investigate the influence of ethnicity/race on folate status indicators in Mexican American, African American, and Caucasian women consuming controlled intakes of folate. Further, the adequacy of the 1998 U.S. folate RDA, 400 µg DFE/d, for sustaining sufficient folate nutriture in women differing in ethnicity/race was assessed.
This is the statistical anlasis

Statistical analysis. Baseline (wk 0) differences in serum folate, RBC folate, and urinary folate (all log-transformed) as well as BMI (untransformed) were analyzed by 1-way ANOVA. If a significant ethnicity/racial effect was detected by ANOVA, Tukey’s Honestly Significant Difference (HSD) test was used for mean separation. For tHcy, normality could not be achieved by data transformation, and the Kruskal-Wallis test was employed.
Differences in serum folate, RBC folate, and urinary folate mean concentrations throughout folate depletion were analyzed by two-factor ANOVA with Tukey’s HSD test for multiple comparisons. The factors were 1) week with 8 levels (wk 0 through wk 7) and 2) ethnic/racial group with 3 levels (Mexican American, African American, and Caucasian). In this analysis, the mean value of the response variable for each ethnic group at each week was used rather than individual subject values. Using the mean emphasizes differences among the ethnic groups, a principal goal of this study, rather than the individual differences within the ethnic groups. For the repletion phase (wk 8–14), a 2-factor ANOVA was used similarly to that used for depletion; however, separate analyses for each folate response variable were performed for the 400 and 800 µg DFE/d groups.

Differences in plasma tHcy among the 3 ethnic groups after folate depletion (wk 7) were analyzed by 1-factor ANOVA. Similarly, differences among ethnic groups after folate repletion (wk 14) were tested by 1-factor ANOVA, but separate analyses were made for the 400 and 800 µg DFE/d groups.

All data summarization and analyses were generated using SAS/STAT software, version 8.2 of the SAS System for Windows (SAS Institute). Significance was set at P 0.05. Data are presented as means (untransformed) ± SEM in the text, table, and figures.
This is the sample selection
Subjects. Women of self-reported Mexican American (n = 14), African American (n = 14), and Caucasian (n = 14) descent, defined as having 2 parents possessing the same ethnicity/race, were selected for participation in this study and were recruited among staff and students at Cal Poly Pomona University and the surrounding community from January 2000 through December 2002. At the initial screening, potential subjects completed a health history questionnaire and gave a fasting blood sample for determination of MTHFR C677T genotype. For those possessing the MTHFR 677 CC genotype, another fasting blood sample was obtained for clinical chemistry evaluation. In addition to the MTHFR 677 CC genotype, inclusion criteria were nonsmoker, nonanemic, not using supplements, no chronic drug or alcohol use, no antifolate medication use, no history of chronic disease, nonpregnant and not planning a pregnancy, nonlactating, and a normal blood chemistry profile. The screening and experimental procedures were reviewed and approved by the Institutional Review Board at Cal Poly Pomona University, and informed consent was obtained from each participant.
http://www.nutrition.org/cgi/content/full/134/7/1786
Moonbear
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Aug20-04, 10:22 AM
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Quote Quote by Monique
You missed the catch phrase
Monique, this study attempted to control for that by providing the same amounts of folate to the women in each group. In that respect, this study seems to be nicely done.

I do have a few issues with it though. The authors acknowledge, and the graphs clearly show that baseline folate was much lower in the African American women, and nothing was done to bring all groups to a similar baseline level, so it's hard to interpret whether all the subsequent differences were due to this baseline difference (i.e., were they never able to "catch up" to the other groups). So, that still could have been a dietary issue prior to the onset of the study.

The other problem I have is they didn't use the correct statistics, so they never actually address directly the differences between groups over time. Instead, for each period of 7 weeks, they averaged together all the results for one group and took a mean for the entire 7 week period that was compared. When they so carefully designed a study that took weekly samples for 14 weeks in the same women, a repeated measures ANOVA is the correct analysis to use. This would have also pulled out information of whether the time to respond to depletion or replacement of folate (i.e., does one group lose folate more rapidly than another) differed and would have answered more definitively whether what appear to be differences on the graphs indeed reached significance. This test would have also factored in change over time to better account for the baseline difference.

They did clearly define how they determined the ethnic/racial groups in this study. They were self-reported and based on having two parents of the same ethnic/racial group.

This study had a very small group size. A total of N=14 for each ethnic/racial group, but they replaced folate back at two levels, and thus further subdivided that number into N=7 for each each ethnic/racial group at each level of folate replacement. On the one hand, obtaining robust significant differences among groups with such small numbers usually means there has to be very little variation within the group. On the other hand, this small group may not have been fully representative of the population at-large, especially since the statistics were not done completely correctly.

Beyond the flaws in the analysis, this is an interesting study. The conclusion it draws may be important in terms of nutrition recommendations, that perhaps the RDA for folate for African American women needs to be higher than for other women (note, this study only included women, so whether the same holds true for men is not addressed). The authors list a number of ailments that are higher in the African American population than among other Americans, and propose that something as simple as folate concentrations may underlie these multiple risks for this population. Certainly, this would have to be borne out by a larger study conducted for a longer time among a larger segment of the population, including men and women in multiple age groups, to determine if folate differences are this common and if increased supplements can correct this depletion if it exists.

What was also interesting is that the Mexican-American women did not appear to differ from Caucasian American women in their responses to the folate depletion/replacement, while the premise for including this group was that there is a higher incidence of neural tube defects in the fetuses/babies of Mexican American women. Neural tube defects are commonly associated with folate deprivation, so it was a reasonable premise. However, in that case, the results don't seem to support that this is the reason, so some other reason needs to be considered, which in that case may be dietary rather than a genetic predisposition to lower folate concentrations in the body.

Overall, don't dismiss a study because it includes different races, as long as the criteria for inclusion into those racial groups is defined clearly. NIH requires that any human clinical studies include multiple racial groups unless there is strong justification not to do so.
Monique
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Aug20-04, 10:36 AM
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Quote Quote by iansmith
Monique, the phrase that you pointed out states the problem not the conclusion.
I know, I already acknowledged that
Evo
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Aug20-04, 11:02 AM
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I think one of the problems is that it is common in the US, in particular, to use the term "race", when "ethnic group" is what they are actually discussing.

I think this article I read yesterday goes along with what Monique was trying to point out.

Don't Base Drug Policy on Race, Geneticists Say

WASHINGTON (Reuters) - Health officials may be wrong in attempts to match health care and especially drugs with race, because genetically there is no such thing, gene experts said on Thursday.

http://cmbi.bjmu.edu.cn/news/0307/130.htm
marcus
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Aug20-04, 12:42 PM
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Quote Quote by Evo
I think one of the problems is that it is common in the US, in particular, to use the term "race", when "ethnic group" is what they are actually discussing.

I think this article I read yesterday goes along with what Monique was trying to point out....
Evo if a doctor bases decisions on what medical tests to run and which medications will be safe partly on the patient's "ethnic group"
that could run into the same objections as if (s)he takes a clue
from the patient's race.

Or a diet consultant, mutatis mutandis

If you define race in a special way then races do not exist.
You stipulate what criteria the concept should meet in order to be valid (like universal agreement among experts) and you find it is not valid.
Similar arguments could probably be used to prove that
ethnic groups do not exist and all humanity belongs to one
ethnic group, and there is insufficient scientific basis for the term
"ethnic group".

BTW Evo, I am curious, you say
"goes along with what Monique was trying to point out.... "
so you must have an idea of what she was trying to point
out in her oneline post to hitssquad "You missed the catch phrase."

Please be frank and explicit. What did you think she was trying to point out? What was catchy about the catch phrase? What did Monique assume that hitssquad was saying by posting link and abstract for that article?
Monique
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Aug20-04, 12:49 PM
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Quote Quote by marcus
BTW Evo, I am curious, you say
"goes along with what Monique was trying to point out.... "
so you must have an idea of what she was trying to point
out in her oneline post to hitssquad "You missed the catch phrase."
*sigh* just how many times do I have to say that was a misunderstanding
Evo
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Aug20-04, 01:05 PM
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Quote Quote by marcus
Evo if a doctor bases decisions on what medical tests to run and which medications will be safe partly on the patient's "ethnic group"
that could run into the same objections as if (s)he takes a clue
from the patient's race.
True, which is why we should avoid such broad classifications when it comes to something as critical as drugs. But, it is a starting point.

Quote Quote by marcus
If you define race in a special way then races do not exist.
Actually, the only scientific information I have seen supports the view that for humans, genetically there is only one race. Here is an exerpt from the Director of Princeton's Genomics Institute explaining it.

Racial differences on the genetic level

Another realization coming from the genome project might have a profound effect on social understanding. "From a scientific perspective," Tilghman said, "there is no such thing as race. You cannot scientifically distinguish a race of people genetically from a different race of people. Now you can find a gene that affects skin color, and you can show that this gene has one form in people of African descent and is different form of people, let's say , of Danish descent. But that's just one little change. That doesn't make them a race. If you look at all the other things in their DNA that determine all the ways in which we're the same, in fact the two DNAs are indistinguishable.

So it seems that there is only one race: the human race. "There are variants," Tilghman said, "and the variants we pay more attention to are the variants that are visible to us. But in fact the variants that probably matter much more than whether your skin is black or your skin is white are variants that predispose you to breast cancer. And those occur in all populations; variants that predispose you to heart disease; variants that predispose you to Alzheimer's disease. And those do not track by race. So the important ones are not the visible ones."

http://www.princeton.edu/~paw/web_ex...atures_05.html

Quote Quote by marcus
You stipulate what criteria the concept should meet in order to be valid (like universal agreement among experts) and you find it is not valid.
Similar arguments could probably be used to prove that
ethnic groups do not exist and all humanity belongs to one
ethnic group, and there is insufficient scientific basis for the term
"ethnic group".
An excellent point. Unfortunately, I don't believe that we can get away from these classifications yet, for a number of reasons. Care needs to be taken, however, since there can be so many variables within the broader classifications.

Quote Quote by marcus
BTW Evo, I am curious, you say
"goes along with what Monique was trying to point out.... "
so you must have an idea of what she was trying to point
out in her oneline post to hitssquad "You missed the catch phrase."

Please be frank and explicit. What did you think she was trying to point out? What was catchy about the catch phrase? What did Monique assume that hitssquad was saying by posting link and abstract for that article?
That variables, such as diet, can make a large difference in the results.

I am rushing off to a meeting (I'm late). I'm going to post this quickly (from the article) and will pick this back up when I return. I have some additional information I want to share.

"Geographical origin (ancestry) appears to be more relevant than a person's self-identified race," Venter wrote in a commentary in Friday's issue of the journal Science.

The FDA agrees that many of the differences can be accounted for by cultural issues and habits, such as diet, but wants racial factors studied so the differences can be better understood.

Venter and Haga agree but say self-reported race is irrelevant. "It would be inaccurate to check off any one box on the U.S. census if you African-American or Caucasian because to some degree we all admixed," Haga said in a telephone interview.

"Six million people have actually changed, between censuses, their racial classification, so we are using social constructs to try and define very important scientific issues," Venter added.

So in theory, guidelines could eventually be issued saying black people should get one drug and whites another. But if a black patient lacks the specific genetic makeup lying behind such theory, he or she might get the wrong drug.

"If there is a genetic variable behind a predisposition to disease among a population, it doesn't mean all those in the population are going to have the disease," Haga said.
"
marcus
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Aug20-04, 01:15 PM
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Quote Quote by Monique
*sigh* just how many times do I have to say that was a misunderstanding
Please be frank about this Monique. Hitssquad simply posted the title and authors and abstract.
You replied: "You missed the catch phrase."

Why did you think he missed the catch phrase?
You must assumed he was trying to make some point by posting
the article.

You evidently were saying that he did not make the point
because he did not notice a reservation in the article.

What point did you assume he was trying to make?

Why did you reply in what appears to be a defensive put-down?

What WAS the misunderstanding you are talking about?
Monique
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Aug20-04, 01:26 PM
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The title of his post is "Race is an important determinant of folate status", the abstract states "It is unclear, however, whether these differences are due to variations in dietary folate intake." The one statement seemed to undermine the other. But the second statement was an introduction, the study apparently proves that the difference cannot be attributed to diet, thus they should better have stated it WAS unclear.

I was at work and quickly wanted to point out the inconsistency, you simply could have corrected me.
selfAdjoint
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Aug20-04, 02:09 PM
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We do need to distinguish, in this thread at least, between "race" and "self-reported race". "Race" would presumably be determined by genetic markers. In a clinical setting, a first estimate of race might be made visually, although of course this is not always possible.
marcus
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Aug20-04, 02:14 PM
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Evo recently posted a quote in the Princeton Alumni Weekly from
Shirley Tilghman the director of Princeton's genome project.

"From a scientific perspective," Tilghman said, "there is no such thing as race. You cannot scientifically distinguish a race of people genetically from a different race of people...."

I would suppose on the contary that races would, by any scientific definition, be precisely those procreative groupings which can be distinguished genetically from one another. These exist.

I gather one should not be too critical of Shirley Tilghman's statement since it was not meant to be taken seriously by fellow scientists. It was for public consumption, devoid of footnotes and precise language. There was no pretense that it was scholarly. When she said "race" she most likely mean "race-as-understood-by-the-audience-of-Princeton-alums", not something technically defined.

We dont know how bright Princeton alums are and it could well be that their concept of a racially distinct human population corresponds to nothing real on the face of the earth. We dont know how they think.

Let's say in Uganda there are two tribes---Hutu and Tutsi.. I propose to say that they are racially different if one can distinguish by a DNA analysis of a blood sample between one group and the other. Maybe they are---maybe they aren't. Think of your own examples.
I believe there are pairs of human groups which can be distinguished by DNA. Perhaps Finns and Maori can be, or maybe they cant. Whatever. Some pairs of groups can, I strongly suspect.

If so, then Shirley Tilghman has no business making the vague and misleading statements that she did. It would be naive to treat her statements as authoritative, in my view (especially when she is talking to an alumni weekly reporter for god sake, alumni give money! you say reassuring things they want to hear)

What I hear in Tilghman's soothing message to the alumni is this subtext:

"From a scientific perspective this is what people need to be told for their own good," Tilghman said, "there is no such thing as raceas the general public imagines it. You cannot scientifically distinguish a race as generally conceived genetically from a different race ...."

A scientists job IMHO is to define race classifications carefully so they correspond to real procreative population groups and to identifiable DNA test results, and so they can be useful to doctors prescribing medicines and dieticians advising pregnant mothers and athletic medicine people
and who all. And also to archeologists figuring out human pre-history.
Much to be learned just from getting a clearer picture of our multiple-trunked and branched human tree.
marcus
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Aug20-04, 02:21 PM
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Quote Quote by Monique
The title of his post is "Race is an important determinant of folate status",...
the title of the paper, written in large and in bold so it could not be missed, was


Ethnicity and race influence the folate status response to controlled folate intakes in young women.

what's the difference between the title of his post and the title which the author's gave their paper?

Did the authors of the paper "miss the catch phrase" in the second sentence of their own abstract?

I do wonder what you were thinking Monique. It came across as a put-down, as if you saw him making an argument and found a flaw in it.
It is the reflex that concerns me.
Nereid
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Aug20-04, 02:21 PM
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This looks like an interesting paper; my first reaction on skimming the abstract was the same as one point Moonbear made - 14 per groups is very small, other than as a pilot, does it say anything at all?

However, in this - and a number of 'the 30' which bobf posted, where apparently similar medical studies were done on a self-selected population group - I keep wondering: "What valid conclusions can be drawn?"

First tho, an obvious point (I do hope Moonbear or Adrenaline or someone who actually works in this field chime in here): the purpose of these medical studies is, directly or indirectly, to allow doctors (etc) to do a better job of returning their patients to good health, keeping them in good health, and advising them of changes in diet, habits, lifestyle, etc which may contribute to them maintaining their good health. In this regard, the detailed mechanisms which play a role in folate status are of less immediate value - if some people need more, then say so; if 'some people' can be determined by asking simple questions such as 'do you have parents or grandparents who came from Mexico', then fine.

Now, to the research itself.

I understand that the human body is a very complex organism, and determining how specific physical (and physiological?) states (statuses?) come to be ('high blood pressure', say) can be quite tricky. There are things which are immediate (I got a fright, my pulse rate went through the roof), daily (more alert in the morning), monthly (periods), seasonal ('winter depression'), stage of life (neonate, infant, child, adolescent, adult, oldie); there's diet, drugs, exercise, social environment (e.g. I've heard that happily married people with no financial worries have ~5 years' greater life expectancy than the others), indoor air, water quality, and on and on; oh, and there's genes too.

There used to be a debate - nature vs nurture - but it's dead now; biology has shown that it's both, and not independently either. Apparently there are genes which can be switched on (or off) by environmental triggers; one's genes can lead one to 'create' an environment (your genes 'drive you' to seek out the 'right' kind of friends), and no doubt much richer and more wonderful things.

So, when Perry et al do research into folate status among three groups of women, to what extent can their results be interpreted as relating to:
- the women's diets (present and past)?
- their social environment (e.g. happy home life, high-stress job)?
- their drug intake? (in the broadest sense of 'drug')
- their fitness? (inc things like level of exercise)
- the influence of all earlier stages of life (which may have set their bodies' folate uptake switches permanently, from an 'indeterminate' one)? - from before birth to menopause
- their genotypes
- complex interactions among a subset (including the full set) of the above?

When a study like this (or more likely, a 20-th generation study with this being only the first) does establish that there appears to be a genetic factor and that the relevant genes appear to be absent in CAs - how could a research project be designed that would find the specific genes responsible? (I would guess that if it's just one gene - as in sickle-cell anemia - it'd be pretty easy to find, through epidemiological (?) studies of families, for example) How can the different actions (and reactions?) of the genes be teased out?
ryokan
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Aug20-04, 02:41 PM
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What is the scientific value of the term race? I think that null.

I believe that Genetics is important to the study of populations with historical, ethnic or cultural purposes (migrations, relationships...)
Likewise, of course, Genetics is essential in the modern Medicine.

But "race" or other synonym don't make sense. We can make as many clusters as we wish, based in cultural, ethnic or genetic variants. And...?

It isn't the same thing to study the genetics of something that to use something with clustering purposes. When we have a polygenic trait, there is a continuum that difficults any clustering purpose, with "intra" variations similar or higher than "inter" variations

Genetics is not made with case - control studies, but by linkage analysis, mapping, and molecular studies. Only for that, its useful the study of "isolated" populations. Isolated for the trait studied, but not as "races".


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