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Previous reports have demonstrated that genetic variations in microRNAs regulome could affect microRNAs-mediated regulation. Therefore, in the present study we were aimed at (1) comparison of microRNA 146-a (miR-146a) peripheral blood mononuclear cells (PBMCs) and plasma levels between diabetic patients and controls, and (2) investigating the possible association of rs2910164 with miR-146a and its related target genes expression and also serum cytokine levels. The study population consisted of 60 subjects including 30 type 2 diabetes (T2D) patients and 30 controls with determined genotypes for rs2910164. The RNA expression levels were determined by real-time PCR. Moreover, TNF-α, IL-6, IL-10 and IL-1β serum levels were measured using ELISA method. Our results showed that the miR-146a expression levels were significantly decreased in PBMCs (P= 0.004) and plasma (P= 0.008) samples of patients with T2D compared to healthy participants. In addition, we observed that IRAK1mRNA expression—but not TLR4, TRAF6and NFĸB—was significantly increased in patients with T2D compared to controls (P= 0.028). The relative expression levels of miR-146a in plasma and PBMCs samples of diabetic patients with the rs2910164 GG genotypes were significantly higher than that in CC (P< 0.05). Moreover, no significant differences were found in miR-146a targets and cytokine levels between the rs2910164 different genotypes. Our study demonstrated that miR-146a circulating levels were significantly elevated in controls compared with T2D patients. In addition, we identified that rs2910164-C allele is associated with reduced expression levels of the miR-146a but not its mRNAs targets and cytokine levels in diabetic patients.

Hypospadias is one of the most common forms of congenital malformation of the male external genitalia worldwide. The ratio in the Iranian population is one in 250 live male births. The conversion of testosterone to dihydrotestosterone (DHT) in the presence of steroid 5α-reductase 2, which is encoded by SRD5A2gene, plays an important role in the normal development of the male reproductive system. We examined whether SRD5A2gene mutations (V89L and A49T polymorphisms) are associated with the risk of hypospadias in the Iranian population. We performed exons sequencing for SRD5A2gene in 109 hypospadias patients. We identified two new mutations in the subgroups of affected cases: including a substitution of the nucleotide T > A in the codon 73 [c.219T > A (p.Leu73_Ser74insHisPro)] and an insertion of an extra A nucleotide in the codon 77 [c.229insA* (p.Gly77*)]. Additionally, we performed PCR–RFLP for the two identified polymorphisms and revealed that V89L [OR = 5.8, 95% CI (3.8–8.8), pvalue < 0.001] and A49T [OR = 10.16, 95% CI (3.94–26.25), pvalue < 0.001] are significantly associated with hypospadias occurrence in patients. Our haplotype analysis further indicated that the Leu–Ala haplotype increases risk of hypospadias; conversely, the Val–Ala haplotype decreases the risk of hypospadias in the studied patients. This study demonstrates that polymorphisms in the SRD5A2gene could be considered as a risk factor for hypospadias disease emergence.

The study was aimed at investigating the association between hsa-mir-27a polymorphism rs895819 (T/C) and type 2 diabetes mellitus (T2DM) susceptibility in a large Iranian cohort. In this case–control study, the investigated population consisted of T2DM patients (n= 204) and sex- and age-matched controls (n= 209). We used the polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP) for genotyping. We observed significant differences between T2DM patients and controls for weight (p= 0.002), BMI (p< 0.001), systolic blood pressure (p< 0.001), diastolic blood pressure (p< 0.001), fasting plasma glucose (p< 0.001), triglyceride (p= 0.004) and LDL cholesterol (p= 0.051). Moreover, we found that genotype distributions were significantly different between groups (p< 0.05) and that the rs895819-C allele is more frequent in controls (p= 0.030, OR = 0.72, 95 % CI 0.53–0.97). Our study shows that rs895819 in hsa-mir-27a is associated with T2DM susceptibility and that the C allele conveyed a protective role against T2DM. Larger multicentric and specific functional studies will be necessary to obtain a deeper comprehension of the role of rs895819 and hsa-mir-27a and how they are involved in the development of diabetes.