HLA associations in South Asian multiple sclerosis

Area of Science:

• Immunogenetics
• Neuroimmunology
• Population Genetics

Background:

• Previous studies on Human Leukocyte Antigen (HLA) associations with multiple sclerosis (MS) in South Asians were limited by sample size.
• Understanding genetic risk factors for MS in diverse populations is crucial for developing targeted prevention and treatment strategies.

Purpose of the Study:

• To identify the primary Human Leukocyte Antigen (HLA) class II alleles associated with multiple sclerosis (MS) in the Indian population.
• To investigate the role of HLA-DRB1, -DQA1, and -DQB1 loci in MS susceptibility among Indians.

Main Methods:

• Genotyping of HLA-DRB1, -DQA1, and -DQB1 alleles using polymerase chain reaction with sequence-specific oligonucleotide probes (PCR-SSOP).
• Analysis included 419 patients with MS and 451 unrelated healthy controls from India.

Main Results:

• Significant association between MS and the HLA gene DRB1 (p=0.0000012) was observed.
• Specific HLA-DRB1 alleles, *15:01 (p=0.00002) and *03 (p=0.00005), were confirmed as risk alleles for MS in Indians.
• Marginal association was found for DQA1 (p=0.04), with no significant association for DQB1 (p=0.26).

Conclusions:

• The study confirms that HLA-DRB1*15:01 and HLA-DRB1*03 alleles confer MS risk in Indians, similar to findings in European populations.
• The lack of association with DQB1 alleles suggests lower linkage disequilibrium with DRB1 risk alleles in this population.
• Fine-mapping of genetic associations in diverse ethnic groups is valuable for understanding population-specific genetic architectures of MS.