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Haplotype-based interaction of the PPARGC1A and UCP1 genes is associated with impaired fasting glucose or type 2 diabetes mellitus.

ABSTRACT: The aim of this study is to evaluate the effect of single-nucleotide polymorphisms (SNPs) of the PPARGC1A and UCP1 genes on impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM) and the haplotype-based interaction between these genes.A cross-sectional study was conducted by cluster sampling in Henan province, China. Based on the level of fasting plasma glucose (FPG) and the history of T2DM, the participants were divided into 2 groups; 83 individuals were in the IFG+DM group (those with IFG or T2DM) and 445 individuals were in the NFPG group (those with normal FPG). Kernel canonical correlation analysis (KCCA), a haplotype-based gene-gene interaction method, which can increase the biological interpretability and extract nonlinear characteristics of SNPs, was used to analyze the correlation and interaction between PPARGC1A and UCP1 genes.The age, BMI, total cholesterol and triglycerides were statistically different between 2 groups (P ? .001). Haplotype analysis showed no significant difference in frequency distribution between the 2 groups when the PPARGC1A or UCP1 gene was tested (P?>?.05). KCCA analysis showed that the maximum kernel canonical correlation coefficient of the PPARGC1A and UCP1 genes was 0.9977 and 0.9995 in the IFG+DM and NPFG groups, respectively. A haplotype-based gene-gene interaction was observed significantly (U?=?-6.28, P?

SUBMITTER: Pei X

PROVIDER: S-EPMC5466206 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Haplotype-based interaction of the PPARGC1A and UCP1 genes is associated with impaired fasting glucose or type 2 diabetes mellitus.

Pei Xiaoting X Liu Li L Cai Jialin J Wei Wenkai W Shen Yan Y Wang Yaxuan Y Chen Yanzi Y Sun Panpan P Imam Mustapha Umar MU Ping Zhiguang Z Fu Xiaoli X

Medicine 20170601 23

The aim of this study is to evaluate the effect of single-nucleotide polymorphisms (SNPs) of the PPARGC1A and UCP1 genes on impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM) and the haplotype-based interaction between these genes.A cross-sectional study was conducted by cluster sampling in Henan province, China. Based on the level of fasting plasma glucose (FPG) and the history of T2DM, the participants were divided into 2 groups; 83 individuals were in the IFG+DM group (those wi ...[more]

PMID: 28591028

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Project description:BACKGROUND:The extent to which diabetes mellitus or hyperglycemia is related to risk of death from cancer or other nonvascular conditions is uncertain. METHODS:We calculated hazard ratios for cause-specific death, according to baseline diabetes status or fasting glucose level, from individual-participant data on 123,205 deaths among 820,900 people in 97 prospective studies. RESULTS:After adjustment for age, sex, smoking status, and body-mass index, hazard ratios among persons with diabetes as compared with persons without diabetes were as follows: 1.80 (95% confidence interval [CI], 1.71 to 1.90) for death from any cause, 1.25 (95% CI, 1.19 to 1.31) for death from cancer, 2.32 (95% CI, 2.11 to 2.56) for death from vascular causes, and 1.73 (95% CI, 1.62 to 1.85) for death from other causes. Diabetes (vs. no diabetes) was moderately associated with death from cancers of the liver, pancreas, ovary, colorectum, lung, bladder, and breast. Aside from cancer and vascular disease, diabetes (vs. no diabetes) was also associated with death from renal disease, liver disease, pneumonia and other infectious diseases, mental disorders, nonhepatic digestive diseases, external causes, intentional self-harm, nervous-system disorders, and chronic obstructive pulmonary disease. Hazard ratios were appreciably reduced after further adjustment for glycemia measures, but not after adjustment for systolic blood pressure, lipid levels, inflammation or renal markers. Fasting glucose levels exceeding 100 mg per deciliter (5.6 mmol per liter), but not levels of 70 to 100 mg per deciliter (3.9 to 5.6 mmol per liter), were associated with death. A 50-year-old with diabetes died, on average, 6 years earlier than a counterpart without diabetes, with about 40% of the difference in survival attributable to excess nonvascular deaths. CONCLUSIONS:In addition to vascular disease, diabetes is associated with substantial premature death from several cancers, infectious diseases, external causes, intentional self-harm, and degenerative disorders, independent of several major risk factors. (Funded by the British Heart Foundation and others.).

Project description:BackgroundPrevious studies indicated that intensive blood pressure (BP) control (systolic BP < 120 mm·Hg) compared with standard BP control (<140 mm·Hg) was associated with an increased risk of type 2 diabetes (T2D) and impaired fasting glucose (IFG) among hypertensive patients with normoglycemia. However, the impact of intensive BP control on the incidence of T2D for those with IFG is still unknown.MethodsThis was a secondary analysis of the SPRINT (Systolic Blood Pressure Intervention Trial) of the study. We included participants with IFG at randomization, which was defined as fasting blood glucose (FBG) between 100 and 125 mg/dL. The primary outcome was incident T2D, defined as events of reaching FBG ≥ 126 mg/dL, participant self-report T2D at annual examination, or a record of hypoglycemic medications at follow-up. The secondary outcome was incident IFG reversion (IFGR), defined as the time to first FBG back to normoglycemia (<100 mg/dl) among participants without incident T2D. Cox proportional hazards models were used to compare the cumulative incidence of outcomes between the two BP control groups. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated.ResultsA total of 3310 participants were included in our primary outcome analysis (median age 67 years, 29% female). There were 293 participants who developed T2D among the intensive BP control group and 256 participants who developed T2D among the standard BP control group, resulting in 56.87 (50.36-63.39) versus 49.33 (43.29-55.37) events per 1000 person-years of treatment (HR 1.18 [95% CI, 1.00-1.40], P=0.052). After excluding 549 participants who developed T2D, 2761 participants were included in our secondary outcome analysis with 559 participants who developed IFGR among the intensive BP control group and 632 participants who developed IFGR among the standard BP control group, resulting in 141.20 (129.50-152.91) versus 158.20 (145.86,170.53) events per 1000 person-years of treatment (HR 0.9 [95% CI, 0.8-1.01], P=0.067).ConclusionsOur study found that in comparison to the standard BP control for hypertensive patients with IFG, intensive BP control was associated with a small increased risk of new-onset T2D, though it did not reach statistical significance. This kind of impact should be considered when implementing the strategy, especially for those with high risks of developing T2D. This trial is registered with NCT01206062.

Dataset Information

Haplotype-based interaction of the PPARGC1A and UCP1 genes is associated with impaired fasting glucose or type 2 diabetes mellitus.

Publications

Haplotype-based interaction of the PPARGC1A and UCP1 genes is associated with impaired fasting glucose or type 2 diabetes mellitus.

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