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Gene From Father May Raise Celiac Disease Risk in Daughters

Celiac.com 04/09/2008 - Do your chances of developing celiac disease vary depending on which parent is passing on the genes? A new study says yes.

According to the results of a recent study, depending on whether the gene is inherited from the father or the mother, and depending on the gender of the child, data suggest that there could be some variance in rates at which the gene is inherited, along with some variance in the rates of celiac disease.

An Italian research team set out to examine risk differences for developing celiac disease between males and females. The research team was made up of Francesca Megiorni, B.Sc., Barbara Mora, B.Sc., Margherita Bonamico, M.D., Maria Barbato, M.D., Monica Montuori, M.D., Franca Viola, M.D., Simonetta Trabace, B.Sc., and Maria C. Mazzilli, B.Sc.

HLA typing in celiac disease is mainly considered for its negative predictive value, as people who do not carry the DQ predisposing molecules are unlikely to develop the disease. Celiac disease occurs twice as often in women as it does in men. In order to learn more about why this might be, the team of researchers recently performed genotyping for HLA-DRB1, DQA1, and DQB1 loci on 281 female and 156 male pediatric celiac patients, 292 nuclear families, and 551 controls. The team then evaluated and compared the odds ratio, parental origin of the disease-associated haplotypes, and transmission ratio distortion between male and female patients.

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Female patients more frequently exhibited DQ2/DQ8 compared to male patients (94% F, 85% M; P = 1.6 Å~ 10−3). The HLA typing test carried a calculated negative predictive value of 99.1% for females and 90.5% for men. Interestingly, the bulk of the 39 DQ2/DQ8 negative cases were male. Looking at the origins of the DQ2 haplotype, the research team noted that 61% of female patients and 42% of male patients carried a paternal combination (P = 0.02).

Looking at the results of the transmission disequilibrium test (TDT) the team noted a major distortion in the DR3-DQ2 transmission from fathers to daughters. Among those patients that are DQ2/DQ8 positive, females showed a higher prevalence of celiac disease than did male patients, with a ratio of 1.8 to 1. Of those patients that were DQ2/DQ8 negative there was a slight tip toward the males, with a ratio of .7 to 1.

The high prevalence of celiac disease in DQ2/DQ8 positive females only applied to females that had inherited the DQ2 haplotype from the father. The results of the study indicate that the sex of the parent supplying the HLA genes may play a role in susceptibility to celiac disease, along with a different effect of parent-specific epigenetic modifications in the two genders.

In all, male patients developed celiac disease more frequently than female patients in absence of HLA predisposing dimmers, but this was due to the occurrence of two DQB1 susceptible alleles that seem to increase the disease risk for males. The results lead the research team to believe that the presence of DQ2 and/or DQ8 molecules is a stronger risk factor in females than in males (ORF = 40.5, ORM = 14.1). Additionally, the results also indicate that HLA typing, which is mainly considered for its negative predictive value in celiac disease, is of greater importance in the testing of females than in males, with calculated negative predictive value of 99.1% and 90.5%, respectively, which points to the need to factor gender into the calculation of disease risk.

These findings, taken together with the revelation that inheritance of a paternal DQ2 haplotype led to celiac predominance in daughters, show that HLA genes play a role in the disease sex bias, and imply a potentially different effect of parent-specific epigenetic modifications in the two genders.

Am J Gastroenterol 2007; 102:1–7

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10 Responses:

 
Amy Baldwin
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said this on
10 Apr 2008 6:23:15 AM PDT
I have suspected that I inherited from my father, this makes sense. My parents have both died as well as my only sister. My brothers are fine and do not have celiac.

 
marcia terrones
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said this on
10 Apr 2008 6:43:02 AM PDT
Very interesting! I am having the Celiac gene testing done right now so this is very newsworthy to me. I'll have to get my father tested if mine comes back positive for DQ2/DQ8.

 
Carol the Dabbler
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said this on
10 Apr 2008 1:20:52 PM PDT
After reading this article all the way through, I scarcely know any more than I did after the headline caught my eye. I have one copy of the DQ8 gene, which I suspect came from my late father (who had many celiac-type symptoms), and would very much like to read a 'translation' of this article written for non-geneticists.

 
Jaymea
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said this on
11 Apr 2008 3:34:27 PM PDT
Me too,I had positive results for DQ2/and or DQ8, and I'm a female - I guess that's revealed by the results if mostly females have those results. I think it came from my paternal line, but not from my dad, but the dad before (granddad). The article is a very good study!

 
Lue Cross
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said this on
11 Apr 2008 6:44:42 PM PDT
I found this article very interesting. I have thought for a long time that my celiac (dx 1997) came from my father. For years before his death in 1976 he complained of stomach problems. He ate large amounts of bread, gravy etc.

 
Robert Reeves
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said this on
12 Apr 2008 3:01:11 PM PDT
As a confirmed celiac for 1 year my youngest daughter has the same symptoms that I had as a child, she is 14 and looks 9 years old. I have already put her on a gluten free diet and I'm waiting now to see if it helps. PS It took 6 months of doctors and tests before they tested me for celiac disease.

 
Kathy Joy
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said this on
12 Apr 2008 7:02:19 PM PDT
I know I have it I was tested my father just died and he had it for many years at least 30 and there were six kids in my family and I lost a sister she may have had his blood type and maybe even had it with different symptoms. She was vomiting all the time. I know I have his blood type and genes. My brother has his blood but has not shown a sign of it yet. I hope he doesn't. I have a son and thank GOD I do not want him to have it. It seems stress brings it on. I have had it for 12 years now.

 
Ruth Walder
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said this on
13 Apr 2008 11:16:57 AM PDT
2 of 3 sisters are biopsy diagnosed. We have suspected that my deceased father had many symptoms as did his mother. Now, I am concerned about my nephews young daughters having the genetic predisposition for Celiac Disease.

 
Astra
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said this on
13 Apr 2008 4:32:49 PM PDT
It is a great article. I am gluten sensitive, so is my father, so was his mother's sister (his mother died young) but I do not have DQ2 OR DQ8. Hope more reliable testing will be developed soon.

 
Terri
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said this on
21 Apr 2008 6:07:09 PM PDT
Great article. My father, deceased at age 40, exhibited at least two of my celiac symptoms, stomach pain and anemia. I am certain that I am celiac because of him, I have two first cousins on my fathers side with it as well...I have not had genetic testing done, but probably should. My daughters tested negative, but what of my grandson's future children?




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So, here goes...my visit with the GI specialist is on Monday. I had tested positive for the IGG antibody and all other bloodwork was negative. I had numerous trips to emerg with stomach pain, lower back pain, tingly tummy, and diarrhea with alternating "c" (I had the word constipation). One diagnosis of diverticulitis, another of IBS, and symptoms continued to get worse....Low B12 for 7 years and abnormal liver (something like hepatocellular disease with cirrhosis). I only have a glass of wine on the weekends...I had been diagnosed in my early 30s with IBS and imodium helped. I also had a rash on my elbows and back and that is when my new GP said maybe it is celiac and she sent me for bloodwork and 3 months later finally get to see the GI specialist. I went gluten free and at first it was hard. It is much easier now...I think at time I give myself contamination because I get some bouts of pain on occasion and I take buscopan and immodium and then I am fine....I am 100% convinced I have celiac but I guess I really do not understand how the rest of the panel would be negative... The rash, the GI symptoms, the B12, and the liver issue all paint a compelling picture...I never thought I would say this but I hope it is truly diagnosed because then I can move forward with a plan. I am down 22 pounds and back at the gym very hard and feeling almost normal for the first time in many years....I also find is so strange that my "gluten" attack usuallys starts with a pins and needs tingly sensation in my back and tummy...I have written a full history and have copies of all my test results so the GI specialist takes me seriously...I read his reviews and they are not good....I understand I will have to do gluten before the endoscopy but that fine...just looking forward to this being partly over...Have a great day!

http://www.cureceliacdisease.org/faqs/ You can also find lots of information on celiac at the University of Chicago celiac site. One test they suggest is the anti EMA antibodies. I don't see that one listed in her results. Probably because it is more expensive to do. So they may have skipped it. The other test they usually do is the total serum IGA levels, which is used to prove that the person's immune system actually makes IgA antibodies. Some people don't make IgA antibodies, so the IgA tests are useless in them. It looks to me like she makes IgA though, if this is the serum IgA result. IgA 133 mg/dl Reference range 33-200 There are also gene tests they can do. The genes indicate the possibility of developing celiac disease, not the automatic presence of celiac disease. About 30% of people in the USA have one of the genes for celiac disease, but only about 1% develop celiac disease. Some of the celiac genes are associated with other autoimmune conditions besides celiac disease. So there are lists of AI associated conditions with celiac disease. Sometimes called related conditions. http://www.drschaer-institute.com/us/celiac-disease/associated-conditions-1051.html

Blood was drawn this afternoon... they said I could get results tomorrow or even the next day! I also have a GI appt scheduled for June 9th. I am so glad I will have at least some kind of answer pretty soon. I'll let you all know. Thanks again for being so helpful!

Thank you so much for those links, I will check into it. Her pediatrician told me this afternoon she is wanting to repeat the bloodwork since that one test was elevated. I'm relieved that her pediatrician didn't dismiss it like the other dr in the practice did.

http://www.houstonceliacs.org/ https://www.csaceliacs.org/csa_chapter_25.jsp You can check with these groups to see if they recommend any doctors in Houston.