Gi Doc Said No Value In Celiac Gene Testing
Posted 21 September 2004 - 04:21 PM
Any input would be greatly appreciated!!!!
Posted 21 September 2004 - 04:46 PM
The gene testing is not specific enough because there are many people who have obvious gluten intolerance and that have symptoms disappear on a gluten free diet that do not have DQ2 or DQ8.
My son is DQ3,3 which is a subset of DQ8 and had classic Celiac symptoms that ALL improved oafter going gluten-free.
It is interesting to know... but beneficial in treatment, not at this time. At least not until they figure out which one's to include or how to break it down even further.
Dr. Fine at Enterolab is the only lab I'm aware of that is testing for other DQ markers, such as DQ1 and DQ3. He has some interesting statements to make on gene testing:
Why are gene results so complicated, and which genes predispose to gluten sensitivity/celiac sprue?
Gene tests for gluten sensitivity, and other immune reactions are HLA (human leukocyte antigen), specifically HLA-DQ, and even more specifically, HLA-DQB1. The nomenclature for reporting HLA gene results has evolved over the last two decades as technology has advanced. Even though the latest technology (and the one we employ at EnteroLab for gene testing) involves sophisticated molecular analysis of the DNA itself, the commonly used terminology for these genes in the celiac literature (lay and medical) reflects past, less specific, blood cell-based (serologic) antigenic methodology. Thus, we report this older "serologic" type (represented by the numbers 1-4, e.g., DQ1, DQ2, DQ3, or DQ4), in addition to the integeric subtypes of these oldest integeric types (DQ5 or DQ6 as subtypes of DQ1; and DQ7, DQ8, and DQ9 as subtypes of DQ3). The molecular nomenclature employs 4 or more integers accounting together for a molecular allele indicated by the formula 0yxx, where y is 2 for DQ2, 3 for any subtype of DQ3, 4 for DQ4, 5 for DQ5, or 6 for DQ6. The x's (which commonly are indicated by 2 more numbers but can be subtyped further with more sophisticated DNA employed methods) are other numbers indicating the more specific sub-subtypes of DQ2, DQ3 (beyond 7, 8, and 9), DQ4, DQ5, and DQ6. It should be noted that although the older serologic nomenclature is less specific in the sense of defining fewer different types, in some ways it is the best expression of these genes because it is the protein structure on the cells (as determined by the serologic typing) that determines the gene's biologic action such that genes with the same serologic type function biologically almost identically. Thus, HLA-DQ3 subtype 8 (one of the main celiac genes) acts almost identically in the body as HLA-DQ3 subtype 7, 9, or other DQ3 sub-subtypes. Having said all this, it should be reiterated that gluten sensitivity underlies the development of celiac sprue. In this regard, it seems that in having DQ2 or DQ3 subtype 8 (or simply DQ8) are the two main HLA-DQ genes that account for the villous atrophy accompanying gluten sensitivity (in America, 90% of celiacs have DQ2 [a more Northern European Caucasian gene], and 9% have DQ8 [a more southern European/Mediterranean Caucasian gene], with only 1% or less usually having DQ1 or DQ3). However, it seems for gluten sensitivity to result in celiac sprue (i.e., result in villous atrophy of small intestine), it requires at least 2 other genes also. Thus, not everyone with DQ2 or DQ8 get the villous atrophy of celiac disease. However, my hypothesis is that everyone with these genes will present gluten to the immune system for reaction, i.e., will be gluten sensitive. My and other published research has shown that DQ1 and DQ3 also predispose to gluten sensitivity, and certain gluten-related diseases (microscopic colitis for DQ1,3 in my research and gluten ataxia for DQ1 by another researcher). And according to my more recent research, when DQ1,1 or DQ3,3 are present together, the reactions are even stronger than having one of these genes alone (like DQ2,2, DQ2,8, or DQ8,8 can portend a more severe form of celiac disease).
Is it possible to tell which parent gave me the celiac or gluten sensitivity gene?
Everyone has two copies (or alleles as they are called scientifically) of every gene in the body; one from mother and one from father. The only way to know if a parent definitely has a gluten sensitive or celiac gene without testing them directly, is if a child has two such genes (having received one from mother and one from father). If only one gluten sensitive or celiac allele is present in a child, there is no way to know if it came from mom or dad. One gene is enough, however, to get clinically significant gluten sensitivity or celiac disease, and from published research, two copies yields an even stronger reaction and hence, potentially more severe gluten-related complications.
If I do not have a gluten sensitive or celiac gene, does that mean my parents/siblings/children do not?
Because everyone has two copies (alleles) of every gene, but a parent only gives one of these genes to each of their offspring (distributed randomly between a parent's two alleles), even if a child does not have a gluten sensitive or celiac gene, one or both parents could have one of these predisposing genes as their other allele. Hence, a person without a predisposing gene could still have parents or siblings with these genes. To be sure, each family individual must be tested to know. (The only certainty with respect to genetic testing is that if a person is found to have two predisposing genes, then every one of his/her children and both parents will have at least one copy of these genes, which is enough to get clinically significant gluten sensitivity or even celiac disease.) Because a child gets one allele from each of their parents, even though a particular person does not have a gluten sensitive gene, their children have a good chance of getting one from the other parent since these genes are very common (see next paragraph).
How common are the gluten sensitivity and celiac genes?
DQ2 is present in 31% of the general American population. DQ8 (without DQ2) is present in another 12%. Thus, the main celiac genes are present in 43% of Americans. Include DQ1 (without DQ2 or DQ8), which is present in another 38%, yields the fact that at least 81% of America is genetically predisposed to gluten sensitivity. (Of those with at least one DQ1 allele, 46% have DQ1,7, 42% have DQ1,1, 11% have DQ1,4, and 1% have DQ1,9.) Of the remaining 19%, most have DQ7,7 (an allele almost identical in structure to DQ2,2, the most celiac-predisposing of genetic combinations) which in our laboratory experience is associated with strikingly high antigliadin antibody titers in many such people. Thus, it is really only those with DQ4,4 that have never been shown to have a genetic predisposition to gluten sensitivity, and this gene combination is very rare in America (but not necessarily as rare in Sub-Saharan Africa or Asia where the majority of the inhabitants are not only racially different from Caucasians, but they rarely eat gluten-containing grains, and hence, gluten-induced disease is rare). Thus, based on these data, almost all Americans, especially those descending from Europe (including Mexico and other Latin states because of the Spanish influence), the Middle East, the Near East (including India), and Russia, are genetically predisposed to gluten sensitivity. (That is why we are here doing what we do!) But be aware that if a person of any race has a gluten sensitive gene, and eats gluten, they can become gluten sensitive.
Hope this helps!
Posted 21 September 2004 - 06:06 PM
Posted 22 September 2004 - 02:35 AM
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