Genome-wide polygenic analysis of multiple sclerosis markers

Objective: to perform a genome-wide polygenic analysis of multiple sclerosis (MS) markers in the ethnic groups of Bashkirs, Russians, and Tatars living in the Republic of Bashkortostan (Russian Federation).

Patients and methods. Genotyping was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism analysis of genes of the human leukocyte differentiation antigens CD6 (rs17824933), CD40 (rs6074022), CD58 (rs2300747), CD86 (rs9282641), transcription factors SOX8 (rs2744148) and ZBTB46 (rs6062314), beta-mannosidase MANBA (rs228614), C-type lectin domain CLEC16A (rs12708716), ribosomal protein S6 kinase B1 RPS6KB1 (rs180515), and long noncoding RNA gene PVT1 (rs759648) in 644 patients with MS and 1408 controls. Multilocus analysis of the disease associations with combinations of genotypes and alleles of the studied polymorphic loci was performed using the APSampler algorithm.

Results and discussion. We determined the distribution of genotype and allele frequencies of the studied polymorphic loci in the ethnic groups of Bashkirs, Russians, and Tatars. We also observed disease associations with CD58 (rs2300747) and RPS6KB1 (rs180515) polymorphic loci in Russian men, CD86 (rs9282641) in Russian, PVT1 (rs759648) in Tatar women, CD40 (rs6074022) in Bashkir men, and identified 19 combinations of genotypes and/or alleles significantly associated with MS.

Conclusion. Based on the genome-wide polygenic analysis of MS markers, we identified ethno- and gender-specific combined markers of the disease susceptibility.

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