Peroxisome proliferator-activated receptor γ C161→T polymorphism and coronary artery disease

Wang, Xing Li; Oosterhof, Janine; Duarte, Natalia

doi:10.1016/s0008-6363(99)00256-4

Cited by 130 publications

(110 citation statements)

References 27 publications

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“…Therefore PPARg is a potential candidate gene for the link between diabetes mellitus and the premature atherosclerosis in patients with diabetes mellitus. This hypothesis is supported by the findings of Wang et al (19), who reported an association of a C161T polymorphism in the PPARg gene with a reduced risk of coronary artery disease in patients with and without diabetes. Moreover, it was recently shown that treatment with troglitazone reduces the neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes suggesting a causal involvement of PPARg in the development of atherosclerotic plaque (31).…”

Section: Discussionsupporting

confidence: 73%

“…We could not confirm this finding in our study population. One explanation for these divergent findings could be that our study was exclusively performed with patients with diabetes, whereas Wang et al (19) mainly studied patients without diabetes. Moreover, the frequency of the C161T polymorphism was lower in our study (Group 1: 12.8%, Group 2: 14.1%) as compared with the C161T frequency (27.7%) reported in the previous study (19).…”

Section: Discussionmentioning

confidence: 88%

“…These data suggest that PPARg is a candidate gene for a possible link between altered lipid and glucose metabolism, such as in patients with diabetes mellitus, and atherosclerosis development. Moreover, it has been recently shown that a C161T polymorphism in the PPARg-2 gene is associated with a reduced risk of coronary artery disease in patients who were consecutively referred for coronary angiography (19). Since it is difficult to assess the potential role of PPARg in atherosclerosis development in clinical studies, we chose the indirect approach, asking whether different PPARg-2 genotypes determine a different individual risk for the development of atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

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Lack of association between peroxisome proliferator-activated receptor-gamma-2 gene variants and the occurrence of coronary heart disease in patients with diabetes mellitus

Blüher

Klemm

Gerike³

et al. 2002

European Journal of Endocrinology

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Objective: Recent evidence indicates that peroxisome proliferator-activated receptor-g (PPARg) is expressed at high levels in foam cells of atherosclerotic lesions, that PPARg agonists may directly modulate vessel wall function and that mutations in the PPARg-2 gene are associated with a reduced risk of coronary artery disease. Methods: We investigated whether known variants in the PPARg-2 gene are associated with the occurrence of coronary heart disease (CHD) in 365 patients with type 2 diabetes, prospectively characterised for the presence or absence of CHD. The Pro115Gln, Pro12Ala, Pro467Leu, Val290Met mutations and two polymorphisms C478T and C161T of the PPARg-2 gene were examined using PCR, denaturing gradient gel electrophoresis and direct sequencing. Results: The distribution of the Pro12Ala, Ala12Ala, C161T and T161T variants was not significantly different between patients with and without CHD, independent of the gender. The Pro12Ala ðP ¼ 0:011Þ and the Ala12Ala ðP ¼ 0:006Þ variant were associated with a higher body mass index (BMI) compared with the Pro12Pro genotype. A multiple logistic regression analysis introducing the typical risk factors for CHD (age, sex, hypertension, smoking, BMI .26 kg/m 2 , elevated low density lipoprotein cholesterol and haemoglobin A 1 c .7%) identified age .60, male gender, hypertension and a higher BMI, but not the PPARg-2 variants, as significant risk factors for CHD in our study groups. Conclusion: The PPARg-2 genotype was not associated with an increased or reduced risk of the occurrence of CHD and can therefore not be regarded as an independent risk factor for CHD in patients with diabetes mellitus.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Lack of association between peroxisome proliferator-activated receptor-gamma-2 gene variants and the occurrence of coronary heart disease in patients with diabetes mellitus

Blüher

Klemm

Gerike³

et al. 2002

European Journal of Endocrinology

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“…24 Interestingly, this study did not consider the Ala allele and found that the protective advantage was mainly among the C1431T heterozygotes, with C1431 and TT homozygous individuals each having evidence of increased disease. Based on our findings, we would predict that individuals homozygous for the T allele would have increased disease because of an increased ratio of T to Ala alleles, whereas CT heterozygotes, in contrast, would be expected to have an approximately equal proportion of opposing Ala alleles and would thus be relatively protected.…”

Section: Discussionmentioning

confidence: 76%

Cardiovascular Risk in Type 2 Diabetes Is Associated With Variation at the PPARG Locus

Doney

Fischer

Leese

et al. 2004

ATVB

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Objective-The Pro12Ala polymorphism of PPARG modulates risk of developing type 2 diabetes. The Ala allele has also been associated with a reduced risk of cardiovascular events. We have shown previously that the linked T allele of the C1431T polymorphism influences Ala12-associated diabetes risk and that the 2 polymorphisms have opposing associations with body weight. We therefore investigated the association of these 2 variants with cardiovascular events in people with type 2 diabetes. T he peroxisome proliferator-activated receptor-␥ (PPAR␥) has a key role in the molecular pathophysiology of obesity and type 2 diabetes. 1 It is directly involved in adipogenesis 2 and liver and muscle responses to glucose, 3,4 as well as some aspects of pancreatic ␤-cell function. 5 It is also the molecular target of the thiazolidinedione class of insulin sensitizing drugs. 6 Genetic variation at the PPARG locus may modulate individual susceptibility to type 2 diabetes mellitus and related traits associated with premature cardiovascular disease. [7][8][9] Notably, the Ala allele of the Pro12Ala polymorphism has been associated with greater insulin sensitivity, 7,9 reduced risk of type 2 diabetes, 10 reduced body mass index (BMI), 11 lower blood pressure, 12 and reduced risk of myocardial infarction. 13 Furthermore, the action of this variant may be subject to interaction with diet and exercise. 14, 15 We demonstrated previously that a further silent variant in exon 6 of PPARG, C1431T, which is in strong linkage disequilibrium (LD) with the Pro12Ala variant, has an opposing association with body mass in several populations with and without type 2 diabetes. 11 We found the Ala12 variant to be associated with a reduced BMI, whereas the T allele was associated with an increased BMI. Similar findings have been reported recently in a study of polycystic ovary syndrome, 16 and several reports have suggested that the T1431 allele is associated with higher leptin levels in obese women. 8,16 Although the relationship between T1431, leptin, and BMI is as yet undefined. Furthermore, we have demonstrated that the strength of the association of the Ala allele with a reduced risk of type 2 diabetes may be modulated by the presence of LD with the T allele. 17 Interestingly, in contrast to the balanced frequency and strong LD observed in the white population, T1431 occurs much more frequently than Ala12 in Asian and Oji-Cree populations, and reports from these populations have suggested a role of T1431 in increased risk of cardiovascular disease. 9,18,19 Because the T allele of C1431T and the Ala allele of Pro12Ala appear to be consistently associated with opposing metabolic traits, we hypothesized this may also be observed for the development of cardiovascular disease in a large group of individuals with type 2 diabetes. Materials and MethodsAll individuals with diabetes mellitus in the population of Tayside, Scotland, have been identified previously through record linkage techniques with a sensitivity of 97%. 20 Health Service data protectio...

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“…Yet the SNP has been reported to be associated with lipoprotein profiles (Wang et al 1999). The interaction effect between the 161C/T variant and apoE-4 genotype on serum cholesterol level has been suggested (Peng et al 2003).…”

Section: Resultsmentioning

confidence: 99%

Single nucleotide variants in the β2-adrenergic and β3-adrenergic receptor genes explained 18.3% of adolescent obesity variation

2005

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Associations of obesity with its candidate genes, b-adrenergic receptor genes (ADRBs), peroxisome proliferator-activated receptor-c (PPARc), and uncoupling proteins (UCPs) were studied in Korean adolescents. We analyzed the obesity-related phenotypes body mass index (BMI), percentage of body fat, plasma leptin and insulin levels, fasting glucose concentration, and plasma lipid profile in 329 teenagers to investigate the effects of seven single nucleotide variants 252G/A, 523C/ A and 1053G/C in ADRB2; Trp64Arg in ADRB3; 161C/ T in PPARc; Ala55Val in UCP2; and 210C/T in UCP3. The 1053G/C polymorphism (P < 0.05) in the ADRB2 gene and the Trp64Arg polymorphism (P < 0.01) in the ADRB3 gene were associated with BMI after adjustment for dietary energy intake. Trp64Arg polymorphism also influenced percentage of body fat (P < 0.01) and plasma leptin level (P < 0.05). Furthermore, significant interaction effects between the 1053G/C and Trp64Arg polymorphisms were observed on BMI (P < 0.01). The polymorphisms of the ADRB2 and ADRB3 genes explained 4.3% and 10.1% of the variation on BMI, and the two loci effect, including their epistasis, explained 18.3%. We concluded that 1053G/C and Trp64Arg polymorphisms of the ADRB genes additively and interactively contributed to the variation of complex adolescent obesity.

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Peroxisome proliferator-activated receptor γ C161→T polymorphism and coronary artery disease

Cited by 130 publications

References 27 publications

Lack of association between peroxisome proliferator-activated receptor-gamma-2 gene variants and the occurrence of coronary heart disease in patients with diabetes mellitus

Lack of association between peroxisome proliferator-activated receptor-gamma-2 gene variants and the occurrence of coronary heart disease in patients with diabetes mellitus

Cardiovascular Risk in Type 2 Diabetes Is Associated With Variation at the PPARG Locus

Single nucleotide variants in the β2-adrenergic and β3-adrenergic receptor genes explained 18.3% of adolescent obesity variation

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