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

Abstract

Multiple sclerosis (MS) is a long-term, immune-mediated disease that affectsthe central nervous system, characterized by gradual myelin degradation and thedevelopment of lesions within the brain and spinal cord. Genetic predisposition,particularly involving human leukocyte antigen (HLA) genes, plays a pivotalrole in MS susceptibility. The HLA-DQB1*05 allele has been hypothesized toinfluence MS risk, though its role in diverse populations remains underexplored.This study investigates the association between the HLA-DQB1*05 allele andMS in the Tehran population, aiming to elucidate its protective or risk-conferring effects in an Iranian context. A case-control study was conductedwith 290 participants, comprising 160 healthy controls and 130 MS patientsdiagnosed according to the McDonald criteria. Peripheral blood samples werecollected, and genomic DNA was extracted using the salting-out method. Thepresence of the HLA-DQB1*05 allele was determined using sequence-specificamplification polymerase chain reaction (SAP-PCR). Statistical analysisrevealed 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 thatneither age (p= 0.41) nor gender (p= 0.53) significantly influenced thisassociation. Further analysis demonstrated a gene-dose effect: homozygouscarriers of HLA-DQB1*05 had twice the protective advantage (OR: 0.15)compared to heterozygotes (OR: 0.30), suggesting allele dosage criticallymodulates MS risk. These findings align with global studies on HLA genes buthighlight population-specific variations, as the protective effect of HLA-DQB1*05 in Tehran contrasts with reports of neutral or risk-conferring effectsin other cohorts. This study provides compelling evidence that HLA-DQB1*05significantly reduces MS susceptibility in the Tehran population, likely throughimmune-modulatory mechanisms. The allele’s dose-dependent protection andpopulation-specific role underscore the importance of genetic context in MSresearch. Future work should explore functional mechanisms and validate thesefindings in larger, multi-ethnic cohorts.