Distinct HLA class I and II genotypes and haplotypes are associated with multiple sclerosis in Bahrain

Abstract

Multiple sclerosis (MS) has become prevalent in the Arabian Gulf area with high incidence in Bahrain due to environmental influences and genetic susceptibilities, but there is a lack of study into human leukocyte antigen (HLA) types in patients with MS in Bahrain. The present study aimed to study the HLA types expressed in MS patients compared with in control subjects. Blood samples from 50 Bahraini patients with MS and 50 Bahraini control subjects' were subjected to HLA tissue typing by polymerase chain reaction using sequence-specific primers. In comparison with those in control subjects, the allele frequencies of HLA class-I antigens A2, A9, A19, B5, B35 and B40 were higher in MS patients. For class II antigens, the allele frequencies of DR3, DR4 and DR16 were higher in MS patients. The allele frequency of DR15 was lower in MS patients than in control subjects but the difference was not statistically significant (P=0.138). The higher prevalence of the HLA-ABDR allele was common among the female patients with MS, in relapse remission stage, in cases with higher expanded disability status scale scores and with disease duration between 4 and 9 years. Haplotype HLA-A2-B40-DR2 exhibited significantly higher frequency in MS patients compared with in control subjects (P=0.03). In conclusion, the results indicated different alleles associated with MS compared with previous reviews. The present study supports the importance of identifying genetic susceptibilities and targets for therapies in specific populations and individuals, to personalize disease management in terms of prediction, protective measures and treatment.

Keywords: alleles; expanded disability status scale; genes; human leukocyte antigen typing; multiple sclerosis; polymerase chain reaction.

Figure 1.

Most frequent HLA-ABDR alleles in MS patients and control subjects. The results revealed that HLA-A19, A9, A2, B5 and DR3 were the highest frequency alleles in MS patients, and HLA-A10 the highest frequency allele in control subjects. Error bars indicate the mean ± standard error of the mean. HLA, human leukocyte antigen; MS, multiple sclerosis; C, control.

Figure 2.

Example electrophoresis gel of PCR products for HLA loci in a patient with multiple sclerosis. Negative control (position H1), HLA-A25 (position H2), HLA-A32 (position C3), HLA-A32 (position G3), HLA-B50 (position B7), HLA-B50 (position C7), HLA-B44 (position H7), HLA-DR4 (position A10), HLA-DR13 (position B11), HLA-DR13 (position B11), HLA-DR53 (position B12), HLA-DR52 (position C12) and HLA-DR13 (position H12). HLA, human leukocyte antigen.

Figure 3.

Example electrophoresis gel of PCR products for HLA loci in a healthy control subject. Negative control (position H1), HLA-A24 (position B1), HLA-A3 (position E1), HLA-B8 (position F4), HLA-B8 (position A5), HLA-B8 (position A6), HLA-B47 (position B6), HLA-B8 (position H6), HLA-B47 (position B7), HLA-DR17 (position C10), HLA-DR15 (position E10), HLA-Bw6 (position H10), HLA-DR51 (position A12), HLA-DR52 (position C12) and HLADR17 (position H12). HLA, human leukocyte antigen.