title: Variants of MicroRNA Genes: Gender-Specific Associations with Multiple Sclerosis Risk and Severity.
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).
authors: Dep. of Molecular Biology and Medical biotechnology, Pirogov Russian National Research Medical University, Moscow 117997, Russia. kiselev.ivan.1991@gmail.com.
authors: Ivan
authors: I
authors: Kiselev
authors: Dep. of Molecular Biology and Medical biotechnology, Pirogov Russian National Research Medical University, Moscow 117997, Russia. vitalina.bashinskaya@gmail.com.|Lab. of Functional Genomics of Cardiovascular Diseases, Russian Cardiology Research and Production Complex, Moscow 121552, Russia. vitalina.bashinskaya@gmail.com.
authors: Vitalina
authors: V
authors: Bashinskaya
authors: Dep. of Molecular Biology and Medical biotechnology, Pirogov Russian National Research Medical University, Moscow 117997, Russia. olga.koulakova@gmail.com.|Lab. of Functional Genomics of Cardiovascular Diseases, Russian Cardiology Research and Production Complex, Moscow 121552, Russia. olga.koulakova@gmail.com.
authors: Olga
authors: O
authors: Kulakova
authors: Dep. of Molecular Biology and Medical biotechnology, Pirogov Russian National Research Medical University, Moscow 117997, Russia. tati.90@mail.ru.
authors: Natalia
authors: N
authors: Baulina
authors: Dep. of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, Moscow 117997, Russia. epopova1980@yandex.ru.
authors: Ekaterina
authors: E
authors: Popova
authors: Dep. of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, Moscow 117997, Russia. boykoan13@gmail.com.
authors: Alexey
authors: A
authors: Boyko
authors: Dep. of Molecular Biology and Medical biotechnology, Pirogov Russian National Research Medical University, Moscow 117997, Russia. olga_favorova@mail.ru.|Lab. of Functional Genomics of Cardiovascular Diseases, Russian Cardiology Research and Production Complex, Moscow 121552, Russia. olga_favorova@mail.ru.
authors: Olga
authors: O
authors: Favorova
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D055815:Young Adult
chemical_list: D035683:MicroRNAs
keywords: MSSS; SNP; association analysis; microRNA; multiple sclerosis; susceptibility