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Diabetes, a leading cause of death globally, has different types, with Type 2 Diabetes Mellitus (T2DM) being the most prevalent one. It has been established that variations in the SLC11A1 gene impact risk of developing infectious, inflammatory, and endocrine disorders. This study is aimed to investigate the association between the SLC11A1 gene polymorphisms (rs3731864 G/A, rs3731865 C/G, and rs17235416 + TGTG/− TGTG) and anthropometric and biochemical parameters describing T2DM. Eight hundred participants (400 in each case and control group) were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) and amplification-refractory mutation system-PCR (ARMS-PCR) methods. Lipid profile, fasting blood sugar (FBS), hemoglobin A1c level, and anthropometric indices were also recorded for each subject. Findings revealed that SLC11A1–rs3731864 G/A, –rs17235416 (+ TGTG/− TGTG) were associated with T2DM susceptibility, providing protection against the disease. In contrast, SLC11A1–rs3731865 G/C conferred an increased risk of T2DM. We also noticed a significant association between SLC11A1–rs3731864 G/A and triglyceride levels in patients with T2DM. In silico evaluations demonstrated that the SLC11A2 and ATP7A proteins also interact directly with the SLC11A1 protein in Homo sapiens. In addition, allelic substitutions for both intronic variants disrupt or create binding sites for splicing factors and serve a functional effect. Overall, our findings highlighted the role of SLC11A1 gene variations might have positive (rs3731865 G/C) or negative (rs3731864 G/A and rs17235416 + TGTG/− TGTG) associations with a predisposition to T2DM.

Changes in pro-inflammatory cytokines are key mechanisms leading to kidney fibrosis. Among microRNAs, miR146 is well studied for its diverse roles in modulating immune responses and inflammation. This paper aims to study the prevalence of three functional miR146a gene polymorphisms (rs2910164 C/G, rs57095329 A/G, and rs6864584 T/C) in diabetic and non-diabetic patients with chronic kidney disease (CKD). One hundred fifty CKD patients (73 men, 77 women, mean age 52.17 years) and 150 healthy controls participated in this case–control study. CKD patients were divided into a diabetic nephropathy group and a non-diabetic group. Genotyping was performed by PCR–RFLP and allele-specific-PCR techniques. We found that rs2910164 C/G and rs57095329 A/G polymorphisms significantly enhanced the risk of CKD under different genetic models. Besides, these variations were associated with increased CKD risk in diabetic and non-diabetic patients. On the contrary, the rs6864584 T/C variant was associated with a decreased risk of CKD in non-diabetic patients. There were no notable changes in p-values after adjustment for age, sex, and body mass index. Although no strong linkage was found between the studied variants. In the meantime, different haplotypes of miR146a polymorphisms were associated with enhanced risk of CKD. In summary, our findings provided evidence for the association of miR146a gene polymorphisms with CKD risk in both diabetic and non-diabetic patients. Further studies on different races with larger sample sizes are needed to confirm the current results.

Single nucleotide polymorphisms within genes encoding microRNAs may alter the expression of microRNAs and their target genes, contributing to the etiology of psychiatric disorders. We aimed to investigate the link between rs4705342T/C and rs4705343T/C polymorphisms in the promoter region of miR-143 and the risk of schizophrenia (SCZ) in a sample of an Iranian population. In this experimental study, a total of 398 subjects were recruited. Genotyping carried out using allele‐specific PCR (AS‐PCR) method. Different bioinformatics databases and Cytoscape V3.4.0 software were used for the analysis of the gene-miRNA interaction network. The genotypic analysis of rs4705342C/T showed that CC genotype in the co-dominant model significantly decreased the risk of SCZ (p

To investigate if single-nucleotide polymorphisms (SNPs) in the NR1H2 gene encoding LXRβ contribute to the development of type-2 diabetes mellitus (T2DM) and whether genotypes of two NR1H2 polymorphisms, rs28514894 and rs2303044, are associated with laboratory characteristics of T2DM patients. A total of 900 subjects (450 T2DM cases and 450 healthy subjects) of Iranian ancestry were genotyped for NR1H2 polymorphisms via ARMS-PCR and PCR-RFLP techniques. Our findings showed a significant correlation between both polymorphisms and increased risk of T2DM. The haplotype analysis showed an association between the C A haplotype with enhanced risk of T2DM. In T2DM patients, the mean level of HbA1C and BUN significantly differed among carriers of CC and TT genotypes of the rs28514894 polymorphism (P = 0.05 and P

MiR-143/145 cluster is a novel transcriptional target of many signaling pathways, with variations within this cluster contributed to the risk of multiple diseases. To date, no data regarding the link between miR143/145 cluster polymorphisms and the risk of developing chronic kidney disease (CKD) has been reported. Hence, we aimed to examine such association in a population of Iranian ancestry. In this preliminary study, 276 CKD patients and 300 unrelated age and sex-matched healthy controls were recruited. Genotyping was performed by PCR-RFLP and allele-specific-PCR methods. Computational analyses were performed to predict the potential effects of the variants. Our findings indicated that rs41291957, rs12659504, and rs353292 polymorphisms were positively associated with CKD, while rs4705342 and rs4705343 polymorphisms demonstrated a significant negative association with the disease. Moreover, a significant association was observed between CC + TC and TT genotypes and CKD stages. We found that AACTT, AATTC, AATTT, GATTC, GATTT, and GGCTT haplotypes significantly enhanced the risk of CKD compared with the Grs41291957AArs12659504Crs353292Trs4705342Trs4705343 haplotype. Computational analysis showed that rs353292, rs4705342, and rs4705343 might alter the binding of the transcription factors in this gene cluster. We found that miR-143/145 cluster polymorphisms were associated with CKD risk in a sample of the Iranian population. Replicated studies on different ethnicities are necessary to investigate the association between these promoter variants and clinical outcomes.

Genetic background is an important risk factor for type 2 diabetes mellitus (T2DM). We designed this study to examine the role of rs12778366 and rs3758391, two functional SIRT1 gene polymorphisms, on the risk of T2DM in an Iranian population. In this case-control study, a total of 813 subjects were enrolled. SNPs were genotyped via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Multiple computational analyses were also performed to examine the potential effects of the studied variants. We found a significant association between rs12778366 polymorphism and an enhanced risk of T2DM under allelic C vs. T (OR = 1.50), codominant TC vs.TT (OR = 1.86), dominant CC + TC vs. TT (OR = 1.65), and over-dominant TC vs. CC + TT (OR = 1.80) genetic models. In contrast, codominant CT vs. CC (OR = 0.54) and dominant CT + TT vs. CC (OR = 0.68) models of rs3758391 polymorphism were correlated with decreased risk of T2DM. Compared to the TC haplotype, we have found that the CC combination significantly enhanced the risk of T2DM by 1.86-fold. Computational analyses indicated that the C allele of rs12778366 might disrupt the binding site of the CEBP transcription factor. SIRT1 rs12778366 and rs3758391 polymorphisms might be associated with T2DM susceptibility in our population. Replications in different races with larger sample sizes are necessary to yield more accurate results.

Type 2 diabetes mellitus (T2DM) is a heterogenic disease with increasing incidence. The SLC30A8 gene encodes an islet zinc transporter (ZnT8), and its variants have been associated with glucose and pro-insulin levels. This study was aimed to examine the effects of a missense variant (rs13266634 C/T), and two 3’UTR variants (rs2466294 C/G and rs2466293 T/C) in SLC30A8 gene on T2DM risk in a south-east Iranian population. In this experiment, 450 patients diagnosed with T2DM and 453 healthy subjects from the same geographic area were enrolled. Genotypes were amplified using the ARMS–PCR method. In silico analyses were performed to determine the effects of the variants on the local structure of mRNA, splicing patterns, and potential miRNA-gene interactions as well. Significant differences were noticed between cases and controls regarding the genotypic and allelic distribution of the studied variants. As regards rs2466293 and rs2466294 variants, enhanced risk of T2DM was found under allelic, dominant, recessive, and codominant models (OR > 1). Besides, different genetic models of rs13266634 were associated with decreased risk of T2DM (OR

Schizophrenia (SCZ) is a multifactorial disorder caused by environmental and genetic factors. Studies have shown that various single-nucleotide polymorphisms (SNPs) in the binding sites of microRNAs contribute to the risk of developing SCZ. We aimed to investigate whether the variants located in the 3′-UTR region of LIF (rs929271T>G) and ATF6B (rs8283G>A) were associated with increased susceptibility to SCZ in a population from the south-east of Iran. In this case-control study, a total of 396 subjects were recruited. SNPs were genotyped via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotyping results showed that the G allele of rs929271 significantly increased the risk of SCZ (OR = 1.58 95%CI = 1.19–2.10, p = 0.001). As for rs929271, the GG genotype of co-dominant (OR = 2.54 95%CI = 1.39–4.64, p = 0.002) and recessive (OR = 2.91 95%CI = 1.77–4.80, p

Keratoconus (KTCN) is a congenital corneal eye disorder which correlates with abnormal distribution of the collagen fiber and causes loss of visual acuity. COLA4A gene has a substantive role in collagen synthesis, whereas KIF26B as a new candidate gene belonging to kinesin superfamily (KIFs) has been suggested to be associated with this disease. So, in this preliminary study, we simultaneously evaluated the effects of two single nucleotide polymorphisms, 222855rs7C/T and rs12407427C/T, on KTCN susceptibility in a sample of Iranian population. The present case–control study consists of 144 patients confirmed with KTCN and 153 healthy controls. The variants are genotyped by using amplification refractory mutation system–polymerase chain reaction method. The findings disclosed that rs2228557C/T and rs12407427C/T polymorphisms significantly increased the risk of KTCN in measured (codominant1; p = 0.0001, codominant2; p = 0.0001, codominant3; p = 0.0006, dominant; p = 0.0001, over-dominant; p = 0.0005) and (codominant1; p = 0.0001, codominant3; p = 0.0005, recessive; p = 0.0001) inheritance patterns, respectively. Our results did prove a statistical association of both rs2228557 and rs12407427 genotypes (TT and CT + CC) and allele (T) with KTCN susceptibility in Iranian population. Further studies in other ethnicities are required to verify our results.

Keratoconus (KC) is thinning of the central cornea. Its etiology is unknown, but it may result from degrading of collagen type IV. The major protein in the cornea is collagen. Matrix metalloproteinase-9 (MMP-9) is able to degrade collagen type IV from the basement membrane and extracellular matrix (ECM). MMP-9 enzymatic activity is inhibited by the tissue inhibitor of metalloproteinase-1 (TIMP-1). In the present study, we sought to investigate and evaluate the effects of single nucleotide polymorphisms in COL4A3, MMP-9, and TIMP-1 on the risk of KC in an Iranian population sample. This case–control study was performed on 140 KC patients and 150 healthy controls. Genotyping of the COL4A3 rs55703767, MMP-9 rs17576, and TIMP-1 rs6609533 polymorphisms was done using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Our findings showed that the rs55703767G/T polymorphism decreased the risk of KC (OR = 0.26, 95% CI = 0.08–0.82, P = 0.022). rs17576A/G, associated with KC and the A allele, was significantly overrepresented in healthy individuals. rs6609533A/G (X-chromosome) increased the risk of KC in females (OR = 2.27, 95% CI = 1.06–4.76, P = 0.036). In males, the allele frequency was not associated with KC risk/protection. This study indicates that in our population, the COL4A3 rs55703767 polymorphism decreased the risk of KC. However, the TIMP-1 rs6609533 polymorphism was associated with an increased risk of KC.