Deciphering the Variants Located in the MIR196A2, MIR146A, and MIR423 with Type-2 Diabetes Mellitus in Pakistani Population.

MicroRNAs (miRNAs) are small non-coding RNA molecules that control the post-transcriptional gene expression. They play a pivotal role in the regulation of important physiological processes. Variations in miRNA genes coding for mature miRNA sequences have been implicated in several diseases. However, the association of variants in miRNAs genes with Type 2 Diabetes Mellitus (T2DM) in the Pakistani population is rarely reported. Therefore, the current study was designed to investigate the association of rs11614913 T/C (MIR196A2), rs2910164 G/C (MIR146A), and rs6505162 C/A (MIR423) in clinicopathological proven T2DM patients and gender-matched healthy controls. The tetra-primer amplification refractory mutation system-polymerase chain (ARMS-PCR) reaction method was used to determine the genotypes and to establish the association of each variant with T2DM through inherited models. In conclusion, the present study showed that variants rs11614913 T/C and rs2910164 G/C were linked with the risk of T2DM. The data suggested that rs11614913 T/C and rs2910164 G/C could be considered as novel risk factors in the pathogenesis of T2DM in the Pakistani population.

Association of MIR146A rs2910164 variation with a predisposition to sporadic breast cancer in a Pakistani cohort.

Single-nucleotide polymorphisms (SNPs) in genes coding for microRNAs (miRNAs) play a pivotal role in the progression of breast cancer (BC). We investigated the association of miR-146a rs2910164 GC polymorphism with the risk of BC in the Pakistani population. The miR-146a rs2910164 polymorphism was genotyped in 300 BC cases and 300 age- and gender-matched healthy controls using T-ARMS-PCR. Genotype and allele frequencies were calculated and the association between genotypes and the risk of BC was calculated by odds ratio (OR) and confidence interval (95%). A significant difference in genotypic frequencies (χ2  = 63.10; P = <0.0001) and allelic frequencies (OR = 0.3955 (0.3132-0.4993); P = < 0.0001) was observed between cases and controls. Furthermore, we also found that miR-146 rs2910164 CC homozygote increased the risk of BC in the dominant (OR = 0.2397 (0.1629-0.3526); P = 0.0001; GG vs. GC + CC) and recessive (OR = 2.803 (1.865-4.213); P = <0.0001; CC vs. GC + GG) inheritance models. In summary, miR-146a rs2910164 GC is significantly associated with BC in the Pakistani population. To our knowledge, this is the first study that assessed MIR146a rs2910164 G > C SNP in Pakistani population. By analyzing the secondary structure of MIR146A variant, a significant structural modification was noted. Study with a larger sample size is needed to further confirm of these findings.