Article

Peroxisome proliferator-activated receptor-gamma2 P12A polymorphism and risk of coronary heart disease in US men and women.

Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Mass, USA.
Arteriosclerosis Thrombosis and Vascular Biology (Impact Factor: 5.53). 09/2005; 25(8):1654-8. DOI: 10.1161/01.ATV.0000171993.78135.7e
Source: PubMed

ABSTRACT Activation of the peroxisome proliferator-activated receptor-gamma (PPARgamma) improves insulin sensitivity and exerts antiatherogenic effects. A common alanine for proline substitution at codon 12 in the PPARG2 gene is related to lower receptor activity. Studies suggest that the A12 allele is associated with reduced risk of type 2 diabetes; however, data on the risk of coronary heart disease (CHD) are scarce and controversial.
We examined the relationship between PPARG2 P12A and CHD risk in women (Nurses' Health Study) and men (Health Professionals Follow-Up Study) in nested case control settings. Among participants free of cardiovascular disease at baseline, 249 women and 266 men developed nonfatal myocardial infarction (MI) or fatal CHD during 8 and 6 years of follow-up, respectively. Using risk-set sampling, controls were selected 2:1 matched on age, smoking, and date of blood draw. The relative risk (RR) of nonfatal MI or fatal CHD of carriers compared with noncarriers of the A12 allele was 1.17 (95% CI, 0.82 to 1.68) among women and 1.44 (95% CI, 1.00 to 2.07) among men (pooled RR, 1.30 [95% CI, 1.00 to 1.67]). We found a significantly increased risk associated with the A12 allele among individuals with a body mass index > or =25 kg/m2 (women: RR, 1.88; 95% CI, 1.01 to 3.50; men: RR, 1.55; 95% CI, 0.92 to 2.60; pooled: RR, 1.68; 95% CI, 1.13 to 2.50) but not among those <25 kg/m2 (pooled RR, 0.86; 95% CI, 0.37 to 1.97; P heterogeneity overweight versus nonoverweight 0.16).
These data do not support the hypothesis that the A12 allele is associated with a decreased risk of CHD. The potential interaction between PPARG2 P12A, overweight, and increased CHD risk needs further evaluation.

0 Followers
 · 
80 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Defect in insulin receptors or insulin signaling pathway is a hallmark of T2DM as it directly affects the endothelium. Coronary artery disease (CAD) being a comorbidity of T2DM, polymorphisms in genes of the insulin signaling pathway may affect an individual’s susceptibility to CAD. The objective of present study was to assess the association of CAD with polymorphisms in three genes of insulin signalling pathway; IRS1(G972R), IRS2 (G1057D) and PPARγ (Pro12Ala, C1431T). Blood samples were collected from 416 subjects of Punjabi origin; 200 CAD patients and 216 normal healthy controls matched for age and sex. For G972R polymorphism, Arg972 (A) allele carriers (GA+AA) had increased risk of CAD (OR: 1.92, CI: 1.13–3.29, P = 0.01) in overall population and in individuals with low BMI, HDL-C, high WHR, waist circumference, normal range of cholesterol and triglycerides. D allele of G1057D polymorphism was associated with increased risk of CAD (OR: 1.44, CI-1.08–1.92, P = 0.01) in overall population as well as in individuals with high BMI, WC, WHR and normal range of triglycerides and cholesterol. For PPARγ variants (Pro12Ala,C1431T), no statistical significant association was observed in the allelic and genotypic frequencies of cases and controls but TT genotype (C1431T) and G allele ( Pro12Ala) conferred protection against CAD in individuals with high cholesterol and normal HDL-C respectively. Statistically significant difference in the different genotypic combinations of IRS1 (G972R) with IRS2 (G1057D) and PPARγ (C1431T) confirmed their role in susceptibility to CAD in Punjabi population from North-west India.
    International Journal of Diabetes in Developing Countries 12/2013; 33(4):192-201. DOI:10.1007/s13410-013-0150-2 · 0.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Coronary heart disease (CHD) is a complex disease resulted from interaction of numerous genetic and environmental factors. It is expected that understanding of complex interaction between genetic factors and environmental factors would contribute to clarifying the pathogenesis of CHD, prevention of diseases by modifying of genetic material and advancing of treatment of diseases. Hyperlipidemia is the primary risk factor for atherosclerosis and CHD. In past years, extensive studies were done on cholesterol levels and the genes that coordinate the effects of cholesterol receptor and transporters. The members of nuclear receptor super family, especially the peroxisome proliferator-activated receptors (PPAR) are the most important regulators in this course. PPARs are potential transcriptional factors that regulate fatty acid and carbohydrate metabolism and are dietary lipid sensors. Three subtypes (alfa, beta/delta, gama) are encoded by separate genes and expressed in different tissues. PPAR alpha regulates the expression of genes related to lipid metabolism, monocyte accumulation and adhesion, and formation of foam cell. In animal model of obesity and diabetes mellitus, PPAR beta/delta is suggested to be a suitable target in hyperlipidemia, increasing HDL-cholesterol and reducing adipose fatty acid storage, triglyceride, fasting insulin levels, and small and dense LDL. Furthermore, it was discovered that PPAR beta/delta activates the oxidation of fatty acid by increasing the expression of genes involved in utilization of fatty acid in heart and skeletal muscles and changing skeletal type fibril from glycolytic to oxidative state. PPAR gamma takes part in the regulation of many target genes expression which involved in adipocyte differentiation, lipid metabolism, and glucose homeostasis. PPAR gamma also appears to possess an immune suppressive function, which could favor an anti-atherosclerotic effect. All above findings together have suggested that PPAR would be a promising candidate gene for obesity and diabetes and subsequently for CHD.
    Turkish Journal of Biochemistry 12/2013; 38(4):372-384. DOI:10.5505/tjb.2013.08760
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Considerable studies have been carried out to investigate the relationship between the polymorphisms of PPARG (Pro12Ala, C161T and C1431T) and serum lipid levels, but the results were inconclusive. Hence, we conducted a meta-analysis to clarify the association. MEDLINE, EMBASE and the Cochrane Library databases were searched systematically. The subgroup analysis was performed based on ethnicity. Seventy-four studies with 54,953 subjects were included in this meta-analysis. In Pro12Ala, the group with the ‘PP’ (C/C genotype) genotype group had lower levels of total cholesterol (TC) (mean difference, MD: −0.02, P < 0.00001; I2 = 28%), low-density lipoprotein cholesterol (LDL-C) (MD: −0.02, P < 0.00001; I2 = 30%) and higher levels of triglyceride (TG) (MD: 0.06, P < 0.00001; I2 = 30%) than the combined ‘PA+AA’ (PA = C/G genotype, AA = G/G genotype) genotype group in Asian population, and the group with the ‘PP’ genotype had higher levels of TG (MD: 0.07, P < 0.02; I2 = 67%) than the combined ‘PA+AA’ genotype group in non-Asian population. No statistically significant differences in the levels of TC, TG, high-density lipoprotein cholesterol, LDL-C were detected between different genotypes in C161T(Asian or non-Asian) and C1431T(Asian) polymorphisms. This meta-analysis was a renewed and confirmed study to assess the association between PPARG polymorphisms and serum lipid levels in Asian and non-Asian populations. There is a prominent association between Pro12Ala polymorphism and the levels of TC, LDL-C and TG in Asian population. No statistically significant differences in serum lipid levels were detected between different genotypes in C161T and C1431T polymorphisms.
    Journal of Cellular and Molecular Medicine 09/2014; 19(1). DOI:10.1111/jcmm.12417 · 3.70 Impact Factor

Preview

Download
0 Downloads
Available from