Novel Genetic Variants of HLA Gene Associated with Thai Behcet’s Disease (BD) Patients Using Next Generation Sequencing Technology

Abstract

Abstract Behcet’s disease (BD) is a recurring inflammatory condition that mostly affects the eyes, mouth, and genitals, with organ involvement in the worst-case scenario. Along with environmental and other patient-related factors, genetic polymorphisms play a huge role in BD. This study aimed to investigate the susceptible genetic variants of HLA gene in 56 Thai BD patients and 192 healthy controls. HLA Genotyping was performed by next-generation sequencing (NGS) using a PacBio kit. The association was calculated by the multivariate logistic regression analysis. We found that the following alleles were found to be associated with BD: HLA-A*26:01:01 (OR=6.02, 95% CI=1.45-22.37, p=0.031), HLA-B*39:01:01 (OR=12.59, 95% CI=1.82-78.50, p=0.005), HLA-B*51:01:01 (OR=3.36, 95% CI=1.18-9.54, p=0.023), HLA-DQB1*05:03:01 (OR=9.35,95%CI=3.72-23.39, p=0.0001), and HLA-DRB1*14:54:01 (OR=32.48, 95% CI=18.11-60.78, p=0.001). When the association analysis was performed for a specific BD phenotype (ocular), HLA-DRB1*14:54:01 (OR=11.67, 95% CI=2.86-47.57, p = 0.001), HLA-B* 51:01:01 (OR=5.47, 95% CI=0.99-90.12, p = 0.05), and HLA-B* 51:01:02 (OR=5.33, 95% CI=1.23-23.06, p = 0.025) alleles had the association with ocular involvement in BD, and the HLA DRB1*14:54:01 (OR=3.35, 95% CI=1-11.99, p = 0.04) allele was found to be linked to vascular involvement in BD patients. In conclusion, for the first time in the Thai population, our study discovered susceptible novel alleles in BD patients such as HLA-A*26:01:01, HLA-B*39:01:01, HLA-B*51:01:01, HLA-DRB1*14:54:01, and HLA-DQB1*05:03:01. This highlights the necessity of genetic testing of the disease's risk alleles to diagnose BD. Despite these alleles have a lower positive predictive value, nearly all the observed risk alleles have significant negative predictive values.