A Genetic-epidemiological Case-control Study of HLA-DQB1*05 and Multiple Sclerosis in Tehran

Multiple sclerosis (MS) is a long-term, immune-mediated disease that affects the central nervous system, characterized by gradual myelin degradation and the development of lesions within the brain and spinal cord. Genetic predisposition, particularly involving human leukocyte antigen (HLA) genes, plays a pivotal role in MS susceptibility. The HLA-DQB1*05 allele has been hypothesized to influence MS risk, though its role in diverse populations remains underexplored. This study investigates the association between the HLA-DQB1*05 allele and MS in the Tehran population, aiming to elucidate its protective or risk-conferring effects in an Iranian context. A case-control study was conducted with 290 participants, comprising 160 healthy controls and 130 MS patients diagnosed according to the McDonald criteria. Peripheral blood samples were collected, and genomic DNA was extracted using the salting-out method. The presence of the HLA-DQB1*05 allele was determined using sequence-specific amplification polymerase chain reaction (SAP-PCR). Statistical analysis revealed a striking disparity in allele frequency: 52.5% of controls carried HLA-DQB1*05, compared to only 14.6% of MS patients (p< 0.001). The odds ratio (OR) for MS risk in allele-negative individuals was 6.46 (95% CI: 3.63-11.50), underscoring a robust protective effect. Chi-square analysis confirmed that neither age (p= 0.41) nor gender (p= 0.53) significantly influenced this association. Further analysis demonstrated a gene-dose effect: homozygous carriers of HLA-DQB1*05 had twice the protective advantage (OR: 0.15) compared to heterozygotes (OR: 0.30), suggesting allele dosage critically modulates MS risk. These findings align with global studies on HLA genes but highlight population-specific variations, as the protective effect of HLA-DQB1*05 in Tehran contrasts with reports of neutral or risk-conferring effects in other cohorts. This study provides compelling evidence that HLA-DQB1*05 significantly reduces MS susceptibility in the Tehran population, likely through immune-modulatory mechanisms. The allele’s dose-dependent protection and population-specific role underscore the importance of genetic context in MS research. Future work should explore functional mechanisms and validate these findings in larger, multi-ethnic cohorts.