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Int. J. Mol. Sci. 2015, 16(8), 20067-20081; doi:10.3390/ijms160820067

Variants of MicroRNA Genes: Gender-Specific Associations with Multiple Sclerosis Risk and Severity

1
Dep. of Molecular Biology and Medical biotechnology, Pirogov Russian National Research Medical University, Moscow 117997, Russia
2
Lab. of Functional Genomics of Cardiovascular Diseases, Russian Cardiology Research and Production Complex, Moscow 121552, Russia
3
Dep. of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, Moscow 117997, Russia
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Charles Brennan
Received: 12 July 2015 / Revised: 4 August 2015 / Accepted: 14 August 2015 / Published: 24 August 2015
(This article belongs to the Special Issue Advances in Multiple Sclerosis)
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Abstract

Multiple sclerosis (MS) is an autoimmune neuro-inflammatory disease arising from complex interactions of genetic, epigenetic, and environmental factors. Variations in genes of some microRNAs—key post-transcriptional regulators of many genes—can influence microRNAs expression/function and contribute to MS via expression changes of protein-coding target mRNA genes. We performed an association study of polymorphous variants of MIR146A rs2910164, MIR196A2 rs11614913, MIR499A rs3746444 MIR223 rs1044165 and their combinations with MS risk and severity. 561 unrelated patients with bout-onset MS and 441 healthy volunteers were enrolled in the study. We observed associations of MS risk with allele MIR223*T and combination (MIR223*T + MIR146A*G/G) carriage in the entire groups and in women at Bonferroni-corrected significance level (pcorr < 0.05). Besides, MIR146A*G/G association with MS was observed in women with nominal significance (pf = 0.025). No MS associations were found in men. A more severe MS course (MSSS value > 3.5) was associated with the carriage of MIR499A*C/T and, less reliably, of MIR499A*C (pcorr = 0.006 and pcorr = 0.024, respectively) and with the carriage of combinations (MIR499A*C/T + MIR196A2*C) and (MIR499A*C + MIR196A2*C) (pcorr = 0.00078 and pcorr = 0.0059, respectively). These associations also showed gender specificity, as they were not significant in men and substantially reinforced in women. The strongest association with MS severity was observed in women for combination (MIR499A*C/T + MIR196A2*C): pcorr = 4.43 × 10−6 and OR = 3.23 (CI: 1.99–5.26). View Full-Text
Keywords: multiple sclerosis; microRNA; SNP; association analysis; susceptibility; MSSS multiple sclerosis; microRNA; SNP; association analysis; susceptibility; MSSS
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Kiselev, I.; Bashinskaya, V.; Kulakova, O.; Baulina, N.; Popova, E.; Boyko, A.; Favorova, O. Variants of MicroRNA Genes: Gender-Specific Associations with Multiple Sclerosis Risk and Severity. Int. J. Mol. Sci. 2015, 16, 20067-20081.

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