Effects of Polymorphisms in Pre-miRNA on Inflammatory Markers in Atrial Fibrillation in Han Chinese.

BACKGROUND:MicroRNA molecules have been identified to play key roles in a broad range of physiological and pathological processes. Polymorphisms in the corresponding sequence space are likely to make a significant con-tribution to phenotypic variation. The aim of this study was to evaluate the pre-miR-146a C/G (rs2910164) and pre-miR-499 T/C (rs3746444) polymorphisms and their putative association with inflammatory markers in AF in Han Chinese. METHODS:A total of 123 participants were enrolled, 65 AF patients were confirmed with electrocardiogram (ECG) or dynamic electrocardiography, 58 normal individuals were assigned to the control group. RESULTS:Genotypes of the pre-miR-146a C/G (rs2910164) and pre-miR-499 T/C (rs3746444) polymorphisms were distinguished using the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The distribution of the pre-miR-146a C/G (rs2910164) genotypes CC, CG, and GG was 33.85%, 52.31%, and 13.84% in the AF group and 37.93%, 51.72%, and 10.35% in the controls, respectively. There was no significant difference in either genotype frequency distributions (p = 0.7973) or allele frequency distributions (p = 0.5411) between these two groups. The distribution of the pre-miR-499 T/C (rs3746444) genotypes TT, TC, and CC was 72.41%, 22.41%, and 5.18% in the controls and 49.23%, 38.46%, and 12.31% in AF subjects, respec-tively (p = 0.0296). The frequency of the C allele in the AF group was significantly higher than that in the control group (31.54% vs. 16.38%, p = 0.0057). Compared with the TT genotype, the C allele carriers (TC+CC genotypes) had a 2.7070-fold increased risk of AF. After being adjusted for age, gender, leucocytes, left atrial dimension, left ventricular ejection fraction, serum levels of lipids, and inflammatory markers, the association persisted (adjusted OR = 2.3387, 95% CI =1.1094 - 4.9300, p = 0.0280). Individuals with TC+CC genotype in pre-miR-499 T/C (rs3746444) had greater serum levels of IL-6 and hs-CRP than did patients with the TT genotype. CONCLUSIONS:Our data support that the pre-miR-499 T/C (rs3746444) polymorphism is associated with AF, and the C allele has increased risk for AF in Han Chinese.

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