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, p < 0.0023), while the HLA-DQB1*03 allele was associated with a protective effect (OR = 0.23, CI: 0.12-0.46, p < 0.0023).

CONCLUSION

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