Association of MTHFR and PPARγ2 gene polymorphisms in relation to type 2 diabetes mellitus cases among north Indian population

Raza, Syed Tasleem; Abbas, Shania; Ahmed, Faisal; Fatima, Jalees; Zaidi, Zeashan Haider; Mahdi, Farzana

doi:10.1016/j.gene.2012.09.072

Cited by 17 publications

(19 citation statements)

References 33 publications

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“…A total of 1089 articles were identified for PPARγ2 Indian population (Vimaleswaran et al 2010;Chauhan et al 2010;Sanghera et al 2008;Sanghera et al 2010;Tripathi et al 2013;Pattanayak et al 2014;Kommoju et al 2014;Raza et al 2012), one case-control study for migrant Indian population (Tai et al 2004), one case-control study for indigenous Srilankans (Hassanali et al 2014), and 13 case-control studies for East Asian population (Ho et al 2012;Omori et al 2008;Deeb et al 1998;Nemoto et al 2002;Tai et al 2004;Wang et al 2009a;Li et al 2008;Lin et al 2010;Hara et al 2000;Horiki et al 2004;Lei et al 2000;Mori et al 2001;Oh et al 2000) . No meta-analysis on ADIPOQ (rs16861194) was performed due to lack of studies in South Asian population (Fig.…”

Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

Implications of critical PPARγ2, ADIPOQ and FTO gene polymorphisms in type 2 diabetes and obesity-mediated susceptibility to type 2 diabetes in an Indian population

et al. 2015

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Peroxisome proliferator-activated receptors (PPARγ), adiponectin (ADIPOQ) and fat mass and obesity-associated gene (FTO) have been reported as a key candidate genes for obesity, type 2 diabetes (T2D) susceptibility and insulin resistance, and we hypothesize that in the background of obesity, the effect of PPARγ2 (rs1801282), ADIPOQ (rs16861194) and FTO (rs9939609) variant could potentially influence T2D susceptibility. To decipher a more accurate estimation toward its population-specific impact of these variants toward susceptibility to T2D, a case-control study, systematic review and a meta-analysis was performed in a South Asian population. A case-control analysis of 518 T2D cases and 518 controls of Karnataka origin were performed to analyze the association of PPARγ2 (rs1801282), ADIPOQ (rs16861194) and FTO (rs9939609) on the risk of T2D. In addition, a systematic review and meta-analysis for PPARγ2 (rs1801282) and FTO (rs9939609) was elucidated from Asian population. Our investigation showed that PPARγ2 (rs1801282) and FTO (rs9939609) are associated with T2D susceptibility. When T2D cohort was further stratified according to the obesity status, PPARγ2 (rs1801282) and FTO (rs9939609) showed association with T2D only in the obese diabetic group and ADIPOQ (rs16861194) showed no difference in risk of susceptibility to the disease. The meta-analysis of PPARγ2 (rs1801282) showed population-specific association for T2D susceptibility as opposed to FTO (rs9939609) which showed no difference in population effect toward T2D susceptibility. In conclusion, our study showed that PPARγ2 (rs1801282) and FTO (rs9939609) variants are associated with T2D susceptibility when associated with adiposity in Indian population.

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Section: Characteristics Of Eligible Studiesmentioning

confidence: 99%

Implications of critical PPARγ2, ADIPOQ and FTO gene polymorphisms in type 2 diabetes and obesity-mediated susceptibility to type 2 diabetes in an Indian population

et al. 2015

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“…Only three studies [21], [43], [57] reported statistical power (76–98%), raising the possibility that other included studies were underpowered, which might lead to inaccuracy in our meta-analysis results. Nearly all included studies examined polymorphism only in the MTHFR gene, even though evidence suggests that this gene may interact with others in conferring risk or protection from diabetes.…”

Section: Discussionmentioning

confidence: 94%

“…In the end, 39 studies were included in the meta-analysis (Fig. 1) [7], [8], [21], [22], [26]–[60]. The main characteristics of the included studies are shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…Many studies, however, included cases with T2DM and serious complications, even when the study purported to assess only the association between the MTHFR SNP and T2DM per se. Therefore we divided the 39 studies into two subgroups: 14 studies that explicitly reported the presence of serious complications among cases or failed to report on such complications at all [8], [21], [22], [27], [28],[30],[43],[45],[46],[48],[50],[51],[58],[60], and 25 studies that explicitly reported the absence of serious complications [7], [26], [29], [31]–[42], [44], [47], [49], [52]–[57], [59]. Meta-analysis of these two subgroups, like the meta-analysis across all included studies, failed to provide clear, consistent evidence that the genotype at MTHFR polymorphism rs1801133 was associated with either increased or reduced risk of T2DM (Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…This discrepancy is doubtless due in part to the wide variation in genotype frequencies at the rs1801133 locus. The TT genotype, for example, is present in 9–13% of Brazilians [20], 15–17% of north Indians [21], 18–20% of Chinese [7], and 20–30% of Turkish [22]. This makes it particularly important to systematically assess the association between this polymorphism and risk of T2DM across a range of ethnicities.…”

Section: Introductionmentioning

confidence: 99%

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Methylenetetrahydrofolate Reductase Gene Polymorphism and Risk of Type 2 Diabetes Mellitus

et al. 2013

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ObjectiveThis review aimed to comprehensively assess the literature examining a possible link between the rs1801133 polymorphism (677C→T) in the gene encoding the methylenetetrahydrofolate reductase (MTHFR) gene and risk of type 2 diabetes mellitus (DM).Research Design and MethodsSeveral research databases were systematically searched for studies examining the genotype at the rs1801133 polymorphism in healthy control individuals and individuals with type 2 DM. Genotype frequency data were examined across all studies and across subsets of studies according to ethnicity and presence of serious DM-related complications. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.ResultsA total of 4855 individuals with type 2 DM and 5242 healthy controls from 15 countries comprising Asian, Caucasian and African ethnicities were found to satisfy the inclusion criteria and included in the review. Genotype at the rs1801133 polymorphism was not consistently associated with either increased or reduced risk of type 2 DM; the OR across all studies was 0.91 (95%CI 0.82 to 1.00) for the C- vs. T-allele, 0.88 (0.75 to 1.03) for CC vs. CT+TT, 0.82 (0.71 to 0.95) for CC vs. TT, and 1.15 (1.03 to 1.29) for TT vs. CC+CT. Similar results were found when the meta-analysis was repeated separately for each ethnic subgroup, and for subgroups with or without serious DM-related complications.ConclusionsThere does not appear to be compelling evidence of an association between the genotype at the rs1801133 polymorphism of the MTHFR gene and risk of type 2 DM.

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Does genetic heterogeneity account for the divergent risk of type 2 diabetes in South Asian and white European populations?

et al. 2014

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Aims/hypothesisSouth Asians are up to four times more likely to develop type 2 diabetes than white Europeans. It is postulated that the higher prevalence results from greater genetic risk. To evaluate this hypothesis, we: (1) systematically reviewed the literature for single nucleotide polymorphisms (SNPs) predisposing to type 2 diabetes in South Asians; (2) compared risk estimates, risk alleles and risk allele frequencies of predisposing SNPs between South Asians and white Europeans; and (3) tested the association of novel SNPs discovered from South Asians in white Europeans.MethodsMEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane registry were searched for studies of genetic variants associated with type 2 diabetes in South Asians. Meta-analysis estimates for common and novel bi-allelic SNPs in South Asians were compared with white Europeans from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium. The population burden from predisposing SNPs was assessed using a genotype score.ResultsTwenty-four SNPs from 21 loci were associated with type 2 diabetes in South Asians after meta-analysis. The majority of SNPs increase odds of the disorder by 15–35% per risk allele. No substantial differences appear to exist in risk estimates between South Asians and white Europeans from SNPs common to both groups, and the population burden also does not differ. Eight of the 24 are novel SNPs discovered from South Asian genome-wide association studies, some of which show nominal associations with type 2 diabetes in white Europeans.Conclusions/interpretationBased on current literature there is no strong evidence to indicate that South Asians possess a greater genetic risk of type 2 diabetes than white Europeans.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-014-3354-1) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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Association of MTHFR and PPARγ2 gene polymorphisms in relation to type 2 diabetes mellitus cases among north Indian population

Cited by 17 publications

References 33 publications

Implications of critical PPARγ2, ADIPOQ and FTO gene polymorphisms in type 2 diabetes and obesity-mediated susceptibility to type 2 diabetes in an Indian population

Implications of critical PPARγ2, ADIPOQ and FTO gene polymorphisms in type 2 diabetes and obesity-mediated susceptibility to type 2 diabetes in an Indian population

Methylenetetrahydrofolate Reductase Gene Polymorphism and Risk of Type 2 Diabetes Mellitus

Does genetic heterogeneity account for the divergent risk of type 2 diabetes in South Asian and white European populations?

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