Ramakrishna Balakrishnan S, Venugopal Giriprasad, Singh Alka, Pugazhendhi Srinivasan, Dutta Sangitanjan, Ahuja Vineet, Makharia Govind K
Institute of Gastroenterology SRM Institutes for Medical Science Chennai India.
Department of Gastroenterology and Human Nutrition All India Institute for Medical Sciences New Delhi India.
JGH Open. 2021 Sep 1;5(10):1190-1196. doi: 10.1002/jgh3.12651. eCollection 2021 Oct.
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.
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.
HLA-DQA105:01 (odds ratio [OR] 8.39, 95% confidence interval [CI] 5.64-12.47) and HLA-DQB102:01 (OR 8.59, 95% CI 5.75-12.83) were the genotypes that showed a risk association with symptomatic CeD. Among the haplotypes, HLA-DQA105:01 ~ HLA-DQB102:01 (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-DQA105:01 ~ HLA-DQB102:01 (OR 2.34, 95% CI 1.61-3.43) was significantly associated with risk of symptomatic disease. The strength of association between the HLA-DQA105:01 ~ HLA-DQB102:01 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.
HLA-DQA105:01 ~ HLA-DQB102:01 (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.
人类白细胞抗原DQ（HLA-DQ）基因型在乳糜泻（CeD）的发生中起允许作用。在这项病例对照研究中，我们使用下一代测序来确定印度患者中与CeD相关的HLA-DQA1和~DQB1基因型及单倍型。
使用长程聚合酶链反应（PCR）从259例有症状的CeD患者（160例典型患者和99例非典型患者）、45例无症状CeD患者、96例潜在CeD患者和300例健康成年人的DNA中扩增HLA-DQA1和~DQB1基因座。扩增子被片段化并在Illumina平台上测序，通过与HLA国际免疫遗传学（IMGT）数据库进行比对来确定等位基因和单倍型。
HLA-DQA105:01（优势比[OR] 8.39，95%置信区间[CI] 5.64 - 12.47）和HLA-DQB102:01（OR 8.59，95% CI 5.75 - 12.83）是与有症状CeD呈风险关联的基因型。在单倍型中，HLA-DQA105:01 ~ HLA-DQB102:01（OR 8.56，95% CI 5.67 - 13.19）与有症状CeD呈强风险关联。当将有症状CeD与亚临床形式（无症状和潜在）CeD进行比较时，HLA-DQA105:01 ~ HLA-DQB102:01（OR 2.34，95% CI 1.61 - 3.43）与有症状疾病风险显著相关。HLA-DQA105:01 ~ HLA-DQB102:01单倍型与CeD表型之间的关联强度呈现出典型>非典型>无症状>潜在CeD的梯度变化。在128例（80%）典型、73例非典型（74%）、27例无症状（60%）和52例潜在CeD参与者中发现了与HLA DQ2和/或8表达一致的基因型。
HLA-DQA105:01 ~ HLA-DQB102:01（单倍型DQ2.5）在印度患者中与有症状CeD呈非常强的风险关联。关联强度呈现出从潜在CeD到典型CeD逐渐增加的梯度变化，这与乳糜泻冰山现象中的表型变化相吻合。
