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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.

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 PST
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 PST
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 PST
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 PST
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 PST
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 PST
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 PST
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 PST
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 PST
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 PST
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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