Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India
Abstract Background and Aim Human Leukocyte Antigen DQ (HLA‐DQ) genotypes play a permissive role in the genesis of celiac disease (CeD). In this case–control study, we used next‐generation sequencing to determine HLA‐DQA1 and ~DQB1 genotypes and haplotypes associated with CeD in Indian patients. Met...
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| Format: | Article |
| Language: | English |
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Wiley
2021-10-01
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| Series: | JGH Open |
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| Online Access: | https://doi.org/10.1002/jgh3.12651 |
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| author | Balakrishnan S Ramakrishna Giriprasad Venugopal Alka Singh Srinivasan Pugazhendhi Sangitanjan Dutta Vineet Ahuja Govind K Makharia |
| author_facet | Balakrishnan S Ramakrishna Giriprasad Venugopal Alka Singh Srinivasan Pugazhendhi Sangitanjan Dutta Vineet Ahuja Govind K Makharia |
| author_sort | Balakrishnan S Ramakrishna |
| collection | DOAJ |
| description | Abstract Background and Aim Human Leukocyte Antigen DQ (HLA‐DQ) genotypes play a permissive role in the genesis of celiac disease (CeD). In this case–control study, we used next‐generation sequencing to determine HLA‐DQA1 and ~DQB1 genotypes and haplotypes associated with CeD in Indian patients. Methods HLA‐DQA1 and ~DQB1 loci were amplified, using long‐range polymerase chain reaction (PCR), from DNA of 259 patients with symptomatic CeD (160 typical and 99 atypical), 45 asymptomatic CeD, 96 potential CeD, and 300 healthy adults. Amplicons were fragmented and sequenced on the Illumina platform, and alleles and haplotypes were assigned by matching against the HLA‐international ImMunoGeneTics (IMGT) database. Results HLA‐DQA1*05:01 (odds ratio [OR] 8.39, 95% confidence interval [CI] 5.64–12.47) and HLA‐DQB1*02:01 (OR 8.59, 95% CI 5.75–12.83) were the genotypes that showed a risk association with symptomatic CeD. Among the haplotypes, HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (OR 8.56, 95% CI 5.67–13.19) showed a strong risk association with symptomatic CeD. When comparing symptomatic CeD with subclinical forms (asymptomatic and potential) CeD, HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (OR 2.34, 95% CI 1.61–3.43) was significantly associated with risk of symptomatic disease. The strength of association between the HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 haplotype and the CeD phenotype showed a gradient in the order typical > atypical > asymptomatic > potential CeD. Genotypes consistent with expression of HLA DQ2 and/or 8 were noted in 128 (80%) typical, 73 atypical (74%), 27 (60%) asymptomatic, and 52 (54%) potential CeD participants. Conclusion HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (haplotype DQ2.5) showed a very strong risk association with symptomatic CeD in Indian patients. The strength of association showed a gradient of increase from potential to typical CeD, coinciding with a phenotypic change in the celiac iceberg. |
| first_indexed | 2024-12-24T05:42:21Z |
| format | Article |
| id | doaj.art-f994b0232ced4db5b7ef30958317abde |
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| issn | 2397-9070 |
| language | English |
| last_indexed | 2024-12-24T05:42:21Z |
| publishDate | 2021-10-01 |
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| spelling | doaj.art-f994b0232ced4db5b7ef30958317abde2022-12-21T17:12:47ZengWileyJGH Open2397-90702021-10-015101190119610.1002/jgh3.12651Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in IndiaBalakrishnan S Ramakrishna0Giriprasad Venugopal1Alka Singh2Srinivasan Pugazhendhi3Sangitanjan Dutta4Vineet AhujaGovind K MakhariaInstitute of Gastroenterology SRM Institutes for Medical Science Chennai IndiaInstitute of Gastroenterology SRM Institutes for Medical Science Chennai IndiaDepartment of Gastroenterology and Human Nutrition All India Institute for Medical Sciences New Delhi IndiaDepartment of Cancer Biology Kansas University Medical Center Kansas Kankas USADepartment of Medicine Guwahati Medical College Guwahati IndiaAbstract Background and Aim Human Leukocyte Antigen DQ (HLA‐DQ) genotypes play a permissive role in the genesis of celiac disease (CeD). In this case–control study, we used next‐generation sequencing to determine HLA‐DQA1 and ~DQB1 genotypes and haplotypes associated with CeD in Indian patients. Methods HLA‐DQA1 and ~DQB1 loci were amplified, using long‐range polymerase chain reaction (PCR), from DNA of 259 patients with symptomatic CeD (160 typical and 99 atypical), 45 asymptomatic CeD, 96 potential CeD, and 300 healthy adults. Amplicons were fragmented and sequenced on the Illumina platform, and alleles and haplotypes were assigned by matching against the HLA‐international ImMunoGeneTics (IMGT) database. Results HLA‐DQA1*05:01 (odds ratio [OR] 8.39, 95% confidence interval [CI] 5.64–12.47) and HLA‐DQB1*02:01 (OR 8.59, 95% CI 5.75–12.83) were the genotypes that showed a risk association with symptomatic CeD. Among the haplotypes, HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (OR 8.56, 95% CI 5.67–13.19) showed a strong risk association with symptomatic CeD. When comparing symptomatic CeD with subclinical forms (asymptomatic and potential) CeD, HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (OR 2.34, 95% CI 1.61–3.43) was significantly associated with risk of symptomatic disease. The strength of association between the HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 haplotype and the CeD phenotype showed a gradient in the order typical > atypical > asymptomatic > potential CeD. Genotypes consistent with expression of HLA DQ2 and/or 8 were noted in 128 (80%) typical, 73 atypical (74%), 27 (60%) asymptomatic, and 52 (54%) potential CeD participants. Conclusion HLA‐DQA1*05:01 ~ HLA‐DQB1*02:01 (haplotype DQ2.5) showed a very strong risk association with symptomatic CeD in Indian patients. The strength of association showed a gradient of increase from potential to typical CeD, coinciding with a phenotypic change in the celiac iceberg.https://doi.org/10.1002/jgh3.12651celiac diseasediarrhea and malabsorptiongastroenterologygeneticsintestinal disorders |
| spellingShingle | Balakrishnan S Ramakrishna Giriprasad Venugopal Alka Singh Srinivasan Pugazhendhi Sangitanjan Dutta Vineet Ahuja Govind K Makharia Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India JGH Open celiac disease diarrhea and malabsorption gastroenterology genetics intestinal disorders |
| title | Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India |
| title_full | Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India |
| title_fullStr | Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India |
| title_full_unstemmed | Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India |
| title_short | Human Leukocyte Antigen DQ (HLA‐DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India |
| title_sort | human leukocyte antigen dq hla dq genotypes and haplotypes and their association with phenotype in patients with celiac disease in india |
| topic | celiac disease diarrhea and malabsorption gastroenterology genetics intestinal disorders |
| url | https://doi.org/10.1002/jgh3.12651 |
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