Effect of the Pro12Ala Variant of the Human Peroxisome Proliferator-Activated Receptor γ2 Gene on Adiposity, Fat Distribution, and Insulin Sensitivity in Japanese Men

Mori, Yusaku; Kim-Motoyama, Hoon; Katakura, Tomiyoshi; Yasuda, Kazuki; Kadowaki, Hiroko; Beamer, Brock A.; Shuldiner, Alan R.; Akanuma, Yasuo; Yazaki, Yoshio; Kadowaki, Takashi

doi:10.1006/bbrc.1998.9421

Cited by 124 publications

(81 citation statements)

References 18 publications

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“…In our study we found an association of the Pro12Ala variant with an increased BMI. In contrast to Japanese men (39), but in accordance with results from previous studies among Caucasians (36,37), the homozygous Ala12Ala variant was also associated with an increased BMI. However, the effect of the Ala12Ala variant seems to be associated with the degree of obesity (37).…”

Section: Discussionsupporting

confidence: 90%

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: 90%

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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“…The present study showed different results on the total cholesterol concentration among Type II diabetic patients from that of the previous study [6], where no effect of the Ala12 allele was found on the total cholesterol concentration in Japanese non-diabetics. As in lipid metabolic index, we used non-HDL rather than LDL cholesterol concentrations, based on the recent report [7].…”

contrasting

confidence: 99%

Mutations of the peroxisome proliferator-activated receptor γ (PPARγ) gene in a Japanese population : the Pro12Ala mutation in PPARγ2 is associated with lower concentrations of serum total and non-HDL cholesterol

et al. 2001

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“…11 It has been associated with a modest reduction in BMI and slightly increased insulin sensitivity in two large Finnish populations and with a reduced prevalence of diabetes in Japanese Americans. 9 In contrast one study did not ®nd an association with markers of adiposity and insulin resistance in a smaller population of Japanese men, 12 two studies did not ®nd an association of this variant with type 2 diabetes in Caucasians 13,14 and one study found a positive relationship with BMI. 15 Given the important role of PPARg as a therapeutic target in metabolic diseases and given the physiologically meaningful data supporting a functional role for the PPARg2 Pro115Gln and Pro12Ala mutations, more independent replications are clearly needed to evaluate the potential impact of those mutations in clinically relevant populations.…”

mentioning

confidence: 91%

The Pro115Gln and Pro12Ala PPAR gamma gene mutations in obesity and type 2 diabetes

et al. 2000

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Effect of the Pro12Ala Variant of the Human Peroxisome Proliferator-Activated Receptor γ2 Gene on Adiposity, Fat Distribution, and Insulin Sensitivity in Japanese Men

Cited by 124 publications

References 18 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

Mutations of the peroxisome proliferator-activated receptor γ (PPARγ) gene in a Japanese population : the Pro12Ala mutation in PPARγ2 is associated with lower concentrations of serum total and non-HDL cholesterol

The Pro115Gln and Pro12Ala PPAR gamma gene mutations in obesity and type 2 diabetes

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