[Multiple sclerosis in the Republic of Bashkortostan: population-specific genetic predictors and the results of a 20-year clinical follow-up study].

OBJECTIVE

Identification of a complex of genetic predictors of multiple sclerosis (MS) based on previously obtained results in genome-wide association studies of disease markers (GWAS markers) in a population of MS patients and healthy individuals of the Republic of Bashkortostan (Russian Federation) using polygenic detection.

MATERIAL AND METHODS

The total study group consisted of 2048 people (641 patients with MS and 1407 healthy individuals) who permanently resided in the Republic of Bashkortostan and belonged to the Bashkir (325), Russian (772) or Tatar (951) nationalities. The analysis of association between MS and polymorphisms previously associated with the disease according to GWAS data was performed. Of the 641 MS patients, 247 were the subject of a 20-year prospective clinical follow-up.

RESULTS

The allele was most significantly associated with MS in Russians (OR=2.00, 5.85·10) and Tatars (OR=2.38, 8.61·10). An increased MS risk in Russians was also associated with the (OR=1.56, 0.007) and (OR=1.61, 0.003) alleles. Meta-analysis confirmed the association of the and alleles with MS in the total group, as well as revealed associations of the and alleles with the disease. Using polygenic analysis, we identified a complex predictor with a pronounced protective effect against MS in the total group (OR=0.34, P=2.65·10).

CONCLUSION

We reproduced the association of eight polymorphisms ( and ) with MS, previously identified in GWAS in European populations. Whole exome or genome sequencing may help to reveal the mechanisms underlying the pathogenesis of MS in populations of the Russian Federation.