Coeliac disease – gluten intolerance

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A comment below about gluten intolerance (which is associated with problems digesting products with wheat) made me curious. In much of Eurasia this would be a serious problem since wheat is the staff of life. Hard numbers are difficult to come by. This is as good as anything else I’ve seen:

Celiac disease affects as many as 1 in 300 people in Italy and southwestern Ireland, but is extremely rare in Africa, Japan, and China…According to a multicenter study in 2003, there is a 1 in 133 chance that people with no risk factors or family history in the U.S. have celiac disease. Additionally, a person’s risk increases to a 1 in 22 chance if they have a first-degree relative with celiac disease and a 1 in 39 chance if they have a second-degree relative…Around 60,000 Americans are diagnosed with celiac disease annually and a total of over 2 million have the disease, making it perhaps the most common genetic disorder in the United States…Celiac disease can occur at any age, and females are more commonly affected than males. Of females presenting during their fertile years, the male to female ratio is almost 3 to 1….

From Wiki:

The vast majority of coeliac patients have one of two types of HLA DQ, a gene that is part of the MHC class II antigen-presenting receptor (also called the human leukocyte antigen) system and distinguishes cells between self and non-self for the purposes of the immune system. There are 7 HLA DQ variants (DQ2 and D4 through 9). Two of these variants-DQ2 and DQ8-are associated with coeliac disease. Every person inherits two copies, one from each parent. The gene is located on the short arm of the sixth chromosome, and as a result of the linkage this locus has been labeled CELIAC1.

Coeliac disease shows incomplete penetrance, as the gene alleles associated with the disease appear in most patients, but are neither present in all cases nor sufficient by themselves cause the disease. Over 95% of coeliac patients have an isoform of DQ2 (DQA1*0501:DQB1*0201 haplotype or more simply DQ2.5) and DQ8 (DQA1*0301:DQB1*0302), which is inherited in families.

Incomplete penetrance might be due to the fact that there are other genetic actors which haven’t been elucidated that are necessary for the emergence of this syndrome. Or, there might be environmental or pathogenic triggers which only affect a minority with the necessary genetic predisposition. But in any case, my first thought was gluten intolerance might be the result of an incomplete selection sweep as populations shifted from hunter-gatherer lifestyles to agricultural ones. I’m skeptical of this since populations in Africa and Australia which don’t have a history of wheat agriculture don’t exhibit this syndrome. Additionally, though wheat agriculture is practiced in north China this was originally a region of millet production. Finally, all the reports suggest massive underestimates of the extent of this condition within the population. Like lactose intolerance this isn’t a disease with a clean set of symptoms which are easy to assay quantitatively (is there a way a metric for stool firmness?). The implication of MHC loci as necessary preconditions makes me wonder if gluten intolerance is simply a low frequency condition which is a byproduct of a disease adaptation on the genes in question which was operant in western Eurasia.

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6 Comments

  1. Incomplete penetrance might be due to the fact that there are other genetic actors which haven’t been elucidated that are necessary for the emergence of this syndrome. Or, there might be environmental or pathogenic triggers which only affect a minority with the necessary genetic predisposition. 
     
    or both. a new study on celiac disease implicated IL2 and IL21. that, plus the linkage to MHC, suggests a strong autoimmune component. could be something like type 1 diabetes or crohn’s disese, where environmental triggers (likely some microorganism) lead to devlopment of the disease in those who are susceptible.

  2. would I be right in saying that these autoimmune diseases– celiac, crohn’s, t1d– are all more common in europeans than africans? Could be a side effect of masive selective pressures on immunity after population density shot up.

  3. Could be a side effect of masive selective pressures on immunity after population density shot up. 
     
    well, eurasian populations seem to have undergone more recent selective sweeps than african ones. though the net fitness of a mutant allele might be + there might not have been enough time for modifiers and what not to clean up all the – side effects (i.e., just an extension of the ‘over clocking’ hypothesis for ashkenazi IQ).

  4. I have heard of Crohns being treated with parasites that downgrade an overactive immune system. Celiac is considered a similar disease, though I wonder if it is more than that. I think we have way too much gluten in our diets. I’m slightly sensitive, but it’s in nearly everything, so I have trouble avoiding it.

  5. A lot of autists/parents of autistic children claim that they/their kids suffer from gluten intolerance and that a lot of their symptoms are relieved (at least partially) if they cut gluten out of their diet. No idea what sort of numbers, though — or how much this has been properly researched: 
     
    http://www.autismweb.com/diet.htm 
     
    http://scholar.google.com/scholar?um=1&tab=ws&hl=en&q=autism%20gluten%20intolerance

  6. Actually now that more studies are being done celiac disease is being found world-wide. I personally believe that the indigenous peoples of the Americas have among the highest rates. Considering their high rates of other auto-immune disease, and their cultivation of only non-gluten grains until the european invasion. It is believed that wheat may have been chosen for cultivation based upon its’ opiate-like effects, because it isn’t one of the most easily cultivated grains. Perhaps the narcotic effect, paired with the lack of food choice made it the “staff of life” in europe. Personally, I consider it the “opiate for the masses.”

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