The association of HLA-DQB1*04 and DQB1*03 with neuromyelitis optica spectrum disorders: A case-control study considering genetic ancestry.

Background: Internationally, specific human leukocyte antigen (HLA) class II alleles have been associated with neuromyelitis optica spectrum disorder (NMOSD) risk.

Objective: To establish the association between HLA class II alleles and NMOSD in a Colombian population, while considering genetic ancestry.

Methods: A multicenter case-control study was conducted with NMOSD patients diagnosed with the 2015 Wingerchuk criteria. HLA-DRB1 and HLA-DQB1 alleles were identified using sequence-specific primer polymerase chain reaction (SSP-PCR). Mitochondrial hypervariable region 1 was amplified, and haplogroups were determined with HaploGrep software. Genomic ancestry was assessed with ancestry-informative markers. Associations between HLA polymorphisms and NMOSD were analyzed using logistic regression models.

Results: In total, 82 patients with NMOSD (mean age 43.8 ± 13.3 years; 83% females) and 164 controls (mean age 36.4 ± 11.5 years; 85% females) were enrolled. Mitochondrial haplogroup frequencies were similar between groups. Ancestry analysis revealed distinct population structures. In multivariable logistic regression, the HLA-DQB1*04 allele was significantly associated with increased NMOSD risk (odds ratio (OR) = 3.16, confidence interval (CI): 1.58-6.34, < 0.0023), while the HLA-DQB1*03 allele was associated with a protective effect (OR = 0.23, CI: 0.12-0.46, < 0.0023).

Conclusion: HLA-DQB1*04 allele may increase susceptibility to NMOSD, while DQB1*03 allele could exert a protective effect in our population.