Dataset Information

Association of RAGE gene polymorphism with Type-2 diabetes mellitus in local population.

ABSTRACT: Objectives:Type-2 diabetes mellitus (T2DM) is an endocrine disease having a significant genetic component. Polymorphisms of many genes may affect hereditary vulnerability of the disease that is characterized by insulin resistance and islet disorder. As the genetic basis of T2DM can vary between ethnic groups, it is important to investigate the genetic link of T2DM in Pakistani populace. This study was aimed to assess the association of receptor for advanced glycation end product (RAGE) gene polymorphism (-429T>C) with Type-2 diabetes mellitus within local populace. Methods:Genomic DNA was isolated by following kit protocol. Genotyping of the RAGE gene was studied by PCR-RFLP on genomic DNA. All research work was done in molecular biochemistry laboratory (MBL), University of Agriculture Faisalabad and Postgraduate Laboratory, The University of Faisalabad, Pakistan from December 2016 to July 2017. Results:We found distribution of -429T>C genotypes between T2DM and healthy controls as 24.7% (tt), 24.7% (Tt) and 50.7% (TT). The outcomes were highly compatible statistically. Conclusion:The techniques of PCR and RFLP when performed simultaneously can be helpful in tracing vital information regarding polymorphism of AGE receptor.

SUBMITTER: Zulfiqar S

PROVIDER: S-EPMC5857018 | biostudies-literature | 2018 Jan-Feb

REPOSITORIES: biostudies-literature

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Association of RAGE gene polymorphism with Type-2 diabetes mellitus in local population.

Zulfiqar Saba S Hussain Fatma F Jamil Amer A Ahmed Nisar N

Pakistan journal of medical sciences 20180101 1

<h4>Objectives</h4>Type-2 diabetes mellitus (T2DM) is an endocrine disease having a significant genetic component. Polymorphisms of many genes may affect hereditary vulnerability of the disease that is characterized by insulin resistance and islet disorder. As the genetic basis of T2DM can vary between ethnic groups, it is important to investigate the genetic link of T2DM in Pakistani populace. This study was aimed to assess the association of receptor for advanced glycation end product (RAGE) g ...[more]

PMID: 29643912

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Project description:This study aims to investigate the relationship between single nucleotide polymorphisms (SNPs) of sex hormone binding globulin (SHBG) and type 2 diabetes mellitus (T2DM) in an Uighur population. One hundred and fourteen T2DM male patients (with a history of diabetes or diagnosed as diabetic by the oral glucose tolerance test) and 173 healthy males from the Uighur ethnic group were included in the study to test the following SNPs of SHBG: rs727428, rs1799941, rs6259, rs6257, rs858521, rs858518, rs3760213, and rs11078701. The body mass index (BMI), blood pressure, and waist circumference, and lipid, glucose, HbA1c, insulin, HOMA-IR, testosterone, and SHBG levels of enrolled individuals were measured. We used the t-test or rank sum test and Chi-square test to analyze the difference and compare numeration data, respectively, between the case and control groups. Comparisons among multiple groups were carried out using analysis of variance, and the correlation between variables was determined by nonparametric Spearman rank correlation analysis; multivariate logistic regression analysis was used to assess the risk of abnormal glucose in the two groups. There was a significant difference (P < 0.05) in BMI, blood pressure, and waist circumference, and lipid, glucose, HbA1c, insulin, and HOMA-IR levels between the case and control groups. The risk factors for diabetes included testosterone (P = 0.042) and SHBG (P = 0.001). The distribution of rs858521 (P = 0.001), rs1799941 (2.3%, P = 0.032), rs6259 (2.5%, P = 0.040), and rs727428 (3.4%, P = 0.016) was significantly different between the case and control groups (P < 0.05). In the control group, there was linkage disequilibrium (LD) between rs727428 and rs6259, while in the case group LD was found among rs858518, rs3760213, rs1799941, and rs6257. The frequency of rs858518-rs3760213-rs1799941-rs6257 haplotype TCGC was significantly different between the two groups (P = 0.033). Both testosterone and SHBGwere found to be risk factors of diabetes in the Uighur population, and SNPs of SHBG may contribute to T2DM.

Project description:Background and Objectives: Nowadays, every tenth adult in the world suffers from diabetes mellitus (DM). Diabetic retinopathy (DR) is the most common microvascular complication of type 2 DM (T2DM) and a leading cause of acquired blindness in middle-aged individuals in many countries. Previous studies have identified associations of several gene polymorphisms with susceptibility to microvascular complications of DM in various worldwide populations. In our study, we aimed to test the hypothesis of the associations of single nucleotide polymorphisms (SNP) of the VEGF (-2549I/D), RAGE (-429T/C and -374T/A), TCF7L2 (rs7903146), and ITGA2 (BglII) genes with a predisposition to DR among T2DM patients in the Kazakhstan population. Materials and Methods: We conducted a case-control study comparing the genotype distribution and allele frequencies between groups of DR patients (N = 94), diabetic patients without DR (N = 94), and healthy controls (N = 51). Genotypes were identified using the PCR-RFLP method. Results: In all cases, the genotype distribution corresponded to the Hardy-Weinberg equilibrium. The groups of diabetic patients with and without DR did not significantly differ in the genotype distribution of the SNPs studied. Differences between both groups of diabetic patients and healthy controls in four out of five SNPs were also not significant. At the same time, both groups of diabetic patients differed significantly from healthy controls in genotype distribution (p = 0.042 and 0.005, respectively) and allele frequencies (p = 0.021 and 0.002, respectively) of the BglII polymorphism in the ITGA2 gene. After adjusting for multiple comparisons, the differences between the group of diabetic patients without DR and the control group remained significant (pBonf = 0.027 for genotypes and pBonf = 0.009 for alleles). The BglII- allele was associated with diabetes: OR = 1.81 [1.09-2.99] for DR patients, and OR = 2.24 [1.34-3.75] for diabetic patients without DR. The association was also observed in the subset of Kazakhs. Conclusions: This study shows that the BglII polymorphism in the ITGA2 gene can be associated with T2DM but not with DR. According to our data, the risk allele for diabetes is the wild BglII- allele, and not the minor BglII+, which is considered as risky for DR.

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Association of RAGE gene polymorphism with Type-2 diabetes mellitus in local population.

Publications

Association of RAGE gene polymorphism with Type-2 diabetes mellitus in local population.

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