Tags

Type your tag names separated by a space and hit enter

HLA-DQ and susceptibility to celiac disease: evidence for gender differences and parent-of-origin effects.
Am J Gastroenterol. 2008 Apr; 103(4):997-1003.AJ

Abstract

BACKGROUND AND AIMS

Celiac disease (CD) is twice as frequent among female than male. Despite the large number of reports on the DQ2/DQ8 association, no systematic studies have investigated a possible different role of the HLA genes in the two genders. We performed case-control and family-based analyses of DR-DQ variants in a pediatric CD cohort with the aim of comparing female to male associations and to investigate the paternal/maternal inheritance of the disease-predisposing haplotypes.

METHODS

A total of 281 female and 156 male pediatric celiac patients, 292 nuclear families, and 551 controls were genotyped for HLA-DRB1, DQA1, and DQB1 loci. Odds ratio, parental origin of the disease-associated haplotypes, and transmission ratio distortion were evaluated in-between male and female cases.

RESULTS

DQ2/DQ8 were more frequent in female than in male patients (94% F, 85% M; P = 1.6 x 10(-3)) with a 99.1% and 90.5% calculated negative predictive value of the HLA test, respectively. Surprisingly, the majority of the 39 DQ2/DQ8 negative cases were male. The analysis of the DQ2 haplotype origin showed that 61% of female patients and 42% of male patients carried a paternal combination (P = 0.02). The transmission disequilibrium test (TDT) proved the major distortion in the DR3-DQ2 transmission from fathers to daughters.

CONCLUSIONS

CD is confirmed to be more prevalent in female than in male (F:M = 1.8) but, in DQ2/DQ8 negative patients, we found an unexpected male excess (F:M = 0.7). Moreover, only the inheritance of a paternal DQ2 haplotype led to a daughters predominance. These data show a role of HLA genes on the disease sex bias and suggest a possible different effect of parent-specific epigenetic modifications in the two genders.

Authors+Show Affiliations

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18177450

Citation

Megiorni, Francesca, et al. "HLA-DQ and Susceptibility to Celiac Disease: Evidence for Gender Differences and Parent-of-origin Effects." The American Journal of Gastroenterology, vol. 103, no. 4, 2008, pp. 997-1003.
Megiorni F, Mora B, Bonamico M, et al. HLA-DQ and susceptibility to celiac disease: evidence for gender differences and parent-of-origin effects. Am J Gastroenterol. 2008;103(4):997-1003.
Megiorni, F., Mora, B., Bonamico, M., Barbato, M., Montuori, M., Viola, F., Trabace, S., & Mazzilli, M. C. (2008). HLA-DQ and susceptibility to celiac disease: evidence for gender differences and parent-of-origin effects. The American Journal of Gastroenterology, 103(4), 997-1003. https://doi.org/10.1111/j.1572-0241.2007.01716.x
Megiorni F, et al. HLA-DQ and Susceptibility to Celiac Disease: Evidence for Gender Differences and Parent-of-origin Effects. Am J Gastroenterol. 2008;103(4):997-1003. PubMed PMID: 18177450.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HLA-DQ and susceptibility to celiac disease: evidence for gender differences and parent-of-origin effects. AU - Megiorni,Francesca, AU - Mora,Barbara, AU - Bonamico,Margherita, AU - Barbato,Maria, AU - Montuori,Monica, AU - Viola,Franca, AU - Trabace,Simonetta, AU - Mazzilli,Maria C, Y1 - 2008/01/02/ PY - 2008/1/8/pubmed PY - 2008/6/5/medline PY - 2008/1/8/entrez SP - 997 EP - 1003 JF - The American journal of gastroenterology JO - Am. J. Gastroenterol. VL - 103 IS - 4 N2 - BACKGROUND AND AIMS: Celiac disease (CD) is twice as frequent among female than male. Despite the large number of reports on the DQ2/DQ8 association, no systematic studies have investigated a possible different role of the HLA genes in the two genders. We performed case-control and family-based analyses of DR-DQ variants in a pediatric CD cohort with the aim of comparing female to male associations and to investigate the paternal/maternal inheritance of the disease-predisposing haplotypes. METHODS: A total of 281 female and 156 male pediatric celiac patients, 292 nuclear families, and 551 controls were genotyped for HLA-DRB1, DQA1, and DQB1 loci. Odds ratio, parental origin of the disease-associated haplotypes, and transmission ratio distortion were evaluated in-between male and female cases. RESULTS: DQ2/DQ8 were more frequent in female than in male patients (94% F, 85% M; P = 1.6 x 10(-3)) with a 99.1% and 90.5% calculated negative predictive value of the HLA test, respectively. Surprisingly, the majority of the 39 DQ2/DQ8 negative cases were male. The analysis of the DQ2 haplotype origin showed that 61% of female patients and 42% of male patients carried a paternal combination (P = 0.02). The transmission disequilibrium test (TDT) proved the major distortion in the DR3-DQ2 transmission from fathers to daughters. CONCLUSIONS: CD is confirmed to be more prevalent in female than in male (F:M = 1.8) but, in DQ2/DQ8 negative patients, we found an unexpected male excess (F:M = 0.7). Moreover, only the inheritance of a paternal DQ2 haplotype led to a daughters predominance. These data show a role of HLA genes on the disease sex bias and suggest a possible different effect of parent-specific epigenetic modifications in the two genders. SN - 1572-0241 UR - https://www.unboundmedicine.com/medline/citation/18177450/HLA_DQ_and_susceptibility_to_celiac_disease:_evidence_for_gender_differences_and_parent_of_origin_effects_ L2 - http://Insights.ovid.com/pubmed?pmid=18177450 DB - PRIME DP - Unbound Medicine ER -