Celiac disease (CD) risk conferred by HLA-DQ2 and DQ8 varies significantly across populations. In north India, where CD is as prevalent as in European populations, reports on the association of HLA-DQ2 and DQ8 with CD are limited. In a north Indian CD case-control cohort (459 CD and 450 controls), known CD-associated risk HLA-DQ alleles, HLA-DQA1*05: 01/02: 01/03: 01 and HLA-DQB1*02/*03: 02, were genotyped using SSP-PCR to uncover their frequency and association with CD. Published dense IlluminaImmunochip genotyping data of the study cohort were used to identify proxy-SNPs for HLA-DQ genotypes and their alleles. We also investigated the correlation between common CD phenotypes and DQ2/8 genotypes. Ninety-nine percent of the CD patients were found to carry HLA-DQ2. 5, DQ2. 2 or 8. HLA-DQA1*05: 01 (OR = 5. 86 4. 39-7. 81, p < 0. 0001) and HLA-DQB1*02 (OR = 16. 61 11. 37-24. 25, p < 0. 0001) were identified as the strongest susceptibility alleles. HLA-DQ2. 5 was present in 92% of patients and conferred the highest CD risk (OR = 29. 01 19. 56-43. 00, p < 0. 00001), while DQ8 appeared protective (OR = 0. 42 0. 25-0. 70, p < 0. 0001). HLA-DQ2. 5/8 and HLA-DQ2. 5/2. 2 were found significantly associated with serum anti-tTG-IgA and skin conditions, respectively, among CD patients. rs1129740, rs9273012 and rs7744001 were identified as proxy-SNPs to efficiently predict the presence/absence of DQ2. 5, DQ2. 2, DQ8 and its alleles. This was the first well-powered study to evaluate the susceptibility of HLA-DQ in CD among the north Indian population. HLA-DQ2. 5 showed a strong association with CD, conferring a higher disease risk, while DQ8 appeared protective, and the contribution of DQ2. 2 was inconclusive. Three proxy-SNPs, rs1129740, rs9273012 and rs7744001, could be utilized to predict HLA-DQ genotypes as a cost-effective alternative for CD risk assessment.
Tiwari et al. (Sun,) studied this question.