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DPP4 Gene Polymorphism Associates With Type 2 Diabetes Mellitus in Older Adults

ABSTRACT: Abstract Genetic variations of the dipeptidyl peptidase 4 enzyme (DPP-4) have been associated with glycemic disorders, especially among older adults. The objective of this study was to investigate the association of a single nucleotide polymorphism on the DPP4 gene with the occurrence of type 2 diabetes mellitus in a sample of older community-dwelling patients. Clinical, anthropometric and physiological characteristics as well as biochemical data related to lipidemia, glycemia and hormonal factors and variables related to the lifestyle were analyzed among 338 individuals aged 60 years and older from two general geriatric outpatient clinics in the Federal District, Brazil. Genotypes related to the polymorphism rs3788979 (A/G) of the DPP4 gene of these patients were determined by conventional polymerase chain reaction followed by enzymatic restriction, whereas the serum levels of DPP-4 were assessed by colorimetric immunoassay. Among the results obtained, there was clear variation in the glycemic levels both in terms of blood glucose and glycosylated hemoglobin according to DPP-4 genotypes, with increased levels between homozygotes for the G allele. However, no association was found between genotypes and occurrence of type 2 diabetes mellitus in patients. No other clinical, biochemical or anthropometric variables were influenced by the polymorphism. In our conditions, there was no association between genotypes and DPP-4 levels. Considering that DPP-4 is involved in the metabolism of incretins and directly interferes with glycemia in organisms, our result corroborates that genetic variations of this enzyme can affect glycemic homeostasis, despite not being determinant for the occurrence of type 2 diabetes mellitus.

SUBMITTER: Alves E

PROVIDER: S-EPMC7740615 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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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.

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DPP4 Gene Polymorphism Associates With Type 2 Diabetes Mellitus in Older Adults

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