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Pharmacogenetic variation of SLC47A1 gene and metformin response in type2 diabetes patients.

ABSTRACT: Type 2 diabetes mellitus is a worldwide epidemic disorder with considerable health and economic consequences. Metformin is one of the most commonly prescribed oral antidiabetic drugs. Pharmacogenetic studies showed that variants in genes related to the pharmacokinetics of metformin were associated with glucose-lowering effect of metformin. The aim of this study was to evaluate pharmacogenetic variation in SLC47A1 (rs2289669) and metformin response in type 2 diabetes patients. Seventy one patients with type 2 diabetes were included in the study. The genotypes were determined by Tetra-ARMS-PCR method. There was a significant association between the study polymorphism and the response to metformin treatment with the highest HbA1C reduction in AG genotype. In the dominant model for A allele (AA+AG vs GG), patients with A allele had highest HbA1C reduction in response to metformin.

SUBMITTER: Mousavi S

PROVIDER: S-EPMC5534524 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Pharmacogenetic variation of <i>SLC47A1</i> gene and metformin response in type2 diabetes patients.

Mousavi Saeedeh S Kohan Leila L Yavarian Majid M Habib Asadollah A

Molecular biology research communications 20170601 2

Type 2 diabetes mellitus is a worldwide epidemic disorder with considerable health and economic consequences. Metformin is one of the most commonly prescribed oral antidiabetic drugs. Pharmacogenetic studies showed that variants in genes related to the pharmacokinetics of metformin were associated with glucose-lowering effect of metformin. The aim of this study was to evaluate pharmacogenetic variation in <i>SLC47A1</i> (rs2289669) and metformin response in type 2 diabetes patients. Seventy one ...[more]

PMID: 28775995

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Project description:ObjectiveThis study aimed to evaluate whether the M420del variants of SLC22A1 (rs72552763) is associated with metformin treatment response in Ethiopian patients with type 2 diabetes mellitus (T2DM).Patients and methodsA prospective observational cohort study was conducted on 86 patients with T2DM who had been receiving metformin monotherapy for <1 year. Patients showing ≥0.5% reduction in HbA1c levels from baseline within 3 months and remained low for at least another 3 months were defined as responders while those patients with <0.5% reduction in HbA1c levels and/or those whom started a new class of glucose-lowering drug(s) because of unsatisfactory reduction were defined as non-responders. In addition, good glycemic control was observed when HbA1c ≤7.0%, and the above values were regarded as poor. Genotyping of rs72552763 SNP was performed using TaqMan® Drug Metabolism Enzyme Genotyping Assay and its association with metformin response and glycemic control were assessed by measuring the change in HbA1c and fasting blood glucose levels using Chi-square, logistic regression and Mann-Whitney U-test. Statistical significance was set at p <0.05.ResultsThe minor allele frequency of the rs72552763 SNP of SLC22A1 was 9.3%. Metformin response was significantly higher in deletion_GAT (del_G) genotypes as compared to the wild-type GAT_GAT (G_G) genotypes. Furthermore, a significantly lower median treatment HbA1 level was found in del_G genotypes as compared to G_G genotypes. However, the association of rs72552763 with metformin response was not replicated at the allele level. In contrast, the minor del_allele was significantly associated with good glycemic control compared to the G_allele, though not replicated at del_G genotypes level.ConclusionThis study demonstrated that metformin response was significantly higher in study participants with a heterozygous carrier of M420del variants of SLC22A1 as compared to the wild-type G_G genotypes after 3 months of treatment.

Project description:IntroductionThe prevalence of periodontal disease is high in diabetes patients worldwide, including Bangladesh. Although associations of periodontal disease outcomes and clinical determinants of diabetes have been investigated, few studies have reported on the relationship between periodontal diseases outcomes with modifiable factors, such as self-care and oral hygiene practices, in patients with diabetes. Moreover, in order to develop targeted strategies, it is also important to estimate their aggregated contribution separately from that of the established sociodemographic and diabetics related clinical determinates. Therefore, this study was performed to elucidate 1) the relationship of diabetes patients' self-care and oral hygiene practices to periodontal disease and 2) the relative contributions of selected factors to periodontal disease outcome in type 2 diabetes patients.MethodsThe data were obtained from the baseline survey of a multicentre, prospective cohort study. A total of 379 adult patients with type 2 diabetes from three diabetic centres in Dhaka, Rajshahi and Barishal, received periodontal examinations using the community periodontal index (CPI) probe, glycated haemoglobin examination, other clinical examinations, and structured questionnaires. Multiple logistics regression analyses were performed to assess the associations between selected factors and prevalence of any periodontal disease and its severity.ResultsMore than half of the participants were female (53.8%) and 66.8% of the total participants was 21-50 years old. The prevalence of any (CPI code 2+3+4; 75.7%) and severe form (CPI code 4; 35.1%) of periodontal disease were high in type 2 diabetes patients. In multivariate analysis, the odds of periodontal disease increased with unfavourable glycaemic control indicated by HbA1c ≥ 7%, and decreased by 64%, 85% and 92% with adherence to recommended diet, physical activity, and oral hygiene practices, respectively. Diabetes self-care practice explained the highest proportion of the variance (13.9%) followed by oral hygiene practices (10.9%) by modelling any periodontal disease versus no disease. Variables of diabetes conditions and oral hygiene practices explained 10.9% and 7.3% of the variance by modelling severe (CPI code 4) or moderate (CPI code 3) forms of periodontal disease versus mild form of periodontal disease. Findings also conferred that while poor diabetes control had an individually adverse association with any form of periodontal diseases and its severity, the risk of diseases was moderated by oral hygiene practices.ConclusionsThis study suggested that, in addition to diabetes-related clinical determinants, self-care practices, and oral hygiene practices must be taken into consideration for prevention and control of periodontal disease in patients with diabetes.

Dataset Information

Pharmacogenetic variation of SLC47A1 gene and metformin response in type2 diabetes patients.

Publications

Pharmacogenetic variation of <i>SLC47A1</i> gene and metformin response in type2 diabetes patients.

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