Dataset Information

The role of the PPARG (Pro12Ala) common genetic variant on type 2 diabetes mellitus risk.

ABSTRACT:

Background

Type 2 diabetes (T2DM) prevalence has been rapidly increasing in the last decades. T2DM pathogenesis is related to insulin resistance and beta-cell dysfunction. Peroxisome proliferator-activated receptor gamma (PPARG) is concerned about T2DM risk through the involvement in adipocyte differentiation and energy homeostasis. The present study aimed to find the risk associated with a common genetic variant (Pro12Ala) of the PPARG gene in the development of T2DM in a group of the Iranian population.

Methods

Totally, 149 patients with T2DM and 96 healthy individuals were recruited in this case-control study. The genotyping of the genetic variant was carried out using the polymerase chain reaction (PCR) followed by Sanger sequencing.

Results

No significant difference is observed between the CG and GG genotypes frequency of the PPARG variant (P = 0.17) in T2DM patient and the control groups. Furthermore, the frequency of the G allele was similar between case and control groups. The Pro12Ala variant may decrease the risk of diabetic retinopathy (DR) which was not statistically significant. Furthermore, the Pro12Ala variant caused a 27% increase in the risk of diabetes nephropathy (DN) among patients with T2DM but was not significant.

Conclusions

Our findings showed that the PPARG variant could not impact on T2DM development and its complications.

SUBMITTER: Hashemian L

PROVIDER: S-EPMC8630345 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The role of the PPARG (Pro12Ala) common genetic variant on type 2 diabetes mellitus risk.

Hashemian Leila L Sarhangi Negar N Afshari Mahdi M Aghaei Meybodi Hamid Reza HR Hasanzad Mandana M

Journal of diabetes and metabolic disorders 20210820 2

<h4>Background</h4>Type 2 diabetes (T2DM) prevalence has been rapidly increasing in the last decades. T2DM pathogenesis is related to insulin resistance and beta-cell dysfunction. <i>Peroxisome proliferator-activated receptor gamma (PPARG)</i> is concerned about T2DM risk through the involvement in adipocyte differentiation and energy homeostasis. The present study aimed to find the risk associated with a common genetic variant (Pro12Ala) of the <i>PPARG</i> gene in the development of T2DM in a ...[more]

PMID: 34900790

Similar Datasets

Project description:We have examined the association of 14 tagging single nucleotide polymorphisms (tagSNPs) in peroxisome proliferator activated receptor-gamma transcripts 1 and 2 (PPARG1 and 2) and 5 tagSNPs in adiponectin (ADIPOQ) genes for their effect on type 2 diabetes mellitus (T2D) risk in Asian Indian Sikhs. A total of 554 T2D cases and 527 normoglycemic controls were examined for association with T2D and other subphenotypes of T2D. With the exception of a strong association of PPARG2/Pro12Ala with T2D (odds ratio, 0.13; 95% confidence interval, 0.03-0.56; P = .0007), no other tagSNP in the PPARG locus revealed any significant association with T2D in this population. Similarly, none of the tagSNPs in the ADIPOQ gene was associated with T2D susceptibility in single-site analysis. However, haplotype analysis provided strong evidence of association of these loci with T2D. Three-site haplotype analysis in the PPARG locus using the 2 marginally associated SNPs (P/rs11715073 and P/rs3892175) in combination with Pro12 Ala (P/rs1801282) revealed a strong association of 1 "risk" (CGC) (P = .003, permutation P = .015) and 1 "protective" (CAC) (P = .001, permutation P = .005) haplotype associated with T2D. However, the major effect still appears to be driven by Pro12Ala, as the association of these haplotypes did not remain significant when analyzed conditional upon Pro12Ala (P = .262). In addition, 2-site haplotype analysis in the ADIPOQ locus using only 2 marginally associated SNPs (AD/rs182052 and AD/rs7649121) revealed a significant protective association of the GA haplotype with T2D (P = .009, permutation P = .026). Multiple linear regression analysis also revealed significant association of an ADIPOQ variant (AD/rs12495941) with total body weight (P = .010), waist (P = .024), and hip (P = .021), although these associations were not significant after adjusting for multiple testing. Our new findings strongly suggest that the genetic variation in PPARG and ADIPOQ loci could contribute to the risk for the development of T2D in Indian Sikhs. Identification of causal SNPs in these important biological and positional candidate genes would help determine the true physiologic significance of these loci in T2D and obesity.

Project description:ObjectiveWe aimed to explore the associations between common genetic risk variants with gestational diabetes mellitus (GDM) risk in Russian women and to assess their utility in the identification of GDM cases.MethodsWe conducted a case-control study including 1,142 pregnant women (688 GDM cases and 454 controls) enrolled at Almazov National Medical Research Centre. The International Association of Diabetes and Pregnancy Study Groups criteria were used to diagnose GDM. A total of 11 single- nucleotide polymorphisms (SNPs), including those in HKDC1 (rs10762264), GCK (rs1799884), MTNR1B (rs10830963 and rs1387153), TCF7L2 (rs7903146 and rs12255372), KCNJ11 (rs5219), IGF2BP2 (rs4402960), IRS1 (rs1801278), FTO (rs9939609), and CDKAL1 (rs7754840) were genotyped using Taqman assays. A logistic regression model was used to calculate odds ratios (ORs) and their confidence intervals (CIs). A simple-count genetic risk score (GRS) was calculated using 6 SNPs. The area under the receiver operating characteristic curve (c-statistic) was calculated for the logistic regression model predicting the risk of GDM using clinical covariates, SNPs that had shown a significant association with GDM in our study, GRS, and their combinations.ResultsTwo variants in MTNR1B (rs1387153 and rs10830963) demonstrated a significant association with an increased risk of GDM. The association remained significant after adjustment for age, pre-gestational BMI, arterial hypertension, GDM in history, impaired glucose tolerance, polycystic ovary syndrome, family history of diabetes, and parity (P = 0.001 and P < 0.001, respectively). After being conditioned by each other, the effect of rs1387153 on GDM predisposition weakened while the effect of rs10830963 remained significant (P = 0.004). The risk of GDM was predicted by clinical variables (c-statistic 0.712, 95 % CI: 0.675 - 0.749), and the accuracy of prediction was modestly improved by adding GRS to the model (0.719, 95 % CI 0.682 - 0.755), and more by adding only rs10830963 (0.729, 95 % CI 0.693 - 0.764).ConclusionAmong 11 SNPs associated with T2D and/or GDM in other populations, we confirmed significant association with GDM for two variants in MTNR1B in Russian women. However, these variants showed limited value in the identification of GDM cases.

Dataset Information

The role of the PPARG (Pro12Ala) common genetic variant on type 2 diabetes mellitus risk.

Background

Methods

Results

Conclusions

Publications

The role of the PPARG (Pro12Ala) common genetic variant on type 2 diabetes mellitus risk.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets