Association of Pro12Ala polymorphism in the peroxisome proliferator–activated receptor γ2 gene with small dense low-density lipoprotein in the general population

Hamada, Taku; Kotani, Kazuhiko; Tsuzaki, Kokoro; Sano, Yoshiko; Murata, Takashi; Takahashi, Masahīko; Sato, Shigeaki; Sakane, Naoki

doi:10.1016/j.metabol.2007.05.017

Cited by 20 publications

(9 citation statements)

References 28 publications

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“…Were PPARγ to be implicated directly, carriage of the lower activity PPARγ-Ala form would be expected to associate with a higher proportion of small LDL particles. This was found to be the case by Hamada et al [47], where PPARG Ala12 carriers had a significantly higher proportion of sdLDL fractions 4–7 independent of lipid concentration. As mentioned previously, dietary intervention studies have shown that variation in dietary fat and CHO can strongly influence expression of the small LDL phenotype [23], with high fat intake associated with an increase in large LDL and decrease in sdLDL.…”

Section: Discussionsupporting

confidence: 60%

PPARγ2 Gene Pro12Ala and PPARα Gene Leu162Val Single Nucleotide Polymorphisms Interact with Dietary Intake of Fat in Determination of Plasma Lipid Concentrations

AlSaleh

Frost²,

Griffin³

et al. 2011

Lifestyle Genomics

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Background/Aims: The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of lipid metabolism, activated by unsaturated fatty acids. We investigated independent and interactive effects of PPARγ2 gene PPARG Pro12Ala (rs1801282) andPPARαgene PPARA Leu162Val (rs1800206) genotypes with dietary intake of fatty acids on concentrations of plasma lipids in subjects of whom 47.5% had metabolic syndrome. Methods: The RISCK study is a parallel design, randomised controlled trial. Plasma lipids were quantified at baseline after a 4-week high saturated fatty acids diet and after three parallel 24-week interventions with reference (high saturated fatty acids), high monounsaturated fatty acids and low-fat diets. Single nucleotide polymorphisms were genotyped in 466 subjects. Results: At baseline, the PPARG Ala12allele was associated with increased plasma total cholesterol (n = 378; p = 0.04), LDL cholesterol (p = 0.05) and apoB (p =0.05) after adjustment for age, gender and ethnicity. At baseline, PPARA Leu162Val × PPARG Pro12Ala genotype interaction did not significantly influence plasma lipid concentrations. After dietary intervention, gene-gene interaction significantly influenced LDL cholesterol (p =0.0002) and small dense LDL as a proportion of LDL (p = 0.005) after adjustments. Conclusions: Interaction between PPARG Pro12Ala and PPARA Leu162Valgenotypes may influence plasma LDL cholesterol concentration and the proportion as small dense LDL after a high monounsaturated fatty acids diet.

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Section: Discussionsupporting

confidence: 60%

PPARγ2 Gene Pro12Ala and PPARα Gene Leu162Val Single Nucleotide Polymorphisms Interact with Dietary Intake of Fat in Determination of Plasma Lipid Concentrations

AlSaleh

Frost²,

Griffin³

et al. 2011

Lifestyle Genomics

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“…Nine cohort studies [12,25,26,27,28,29,30,31,32], 7 population case-control studies [33,34,35,36,37,38,39], 31 cross-sectional studies [5,7,10,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67], and 9 interventional studies [8,68,69,70,71,72,73,74,75] were included in the meta-analysis of the association between PPARγ Pro12Ala polymorphism and obesity. The characteristics and results of the studies are summarized in table 1.…”

Section: Resultsmentioning

confidence: 99%

“…Each dataset was treated as a separate comparison in the meta-analysis. Forty studies were on Caucasians [5,8,10,12,25,26,27,28,29,32,33,34,35,36,37,38,39,41,42,43,45,46,47,48,52,53,54,57,60,61,62,63,64,65,66,67,68,69,70], 10 studies were on Asian [31,40,49,50,55,56,58,59,71,72] and 6 studies were on mixed populations [7,30,37,73,74,75]. Between 56 studies, 19 studies provided data on male [10,12,29,33,35,37,40,42,43,47,50,57,60,61,62,65,66,69,71] and 22 studies on female members [10,12,29,32,37,41,42,50,53,54,55,59,60,61,62,64,66,…”

Section: Resultsmentioning

confidence: 99%

Obesity and Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor-Gamma Gene in Healthy Adults: A Systematic Review and Meta-Analysis

et al. 2015

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Background: The aim of this systematic review was to evaluate the relationship between obesity and peroxisome proliferator-activated receptor-gamma (PPARγ) Pro12Ala polymorphism in healthy adults. Summary: Weighted mean differences (WMDs) of body mass index (BMI) were calculated for different inheritance models and subgroups. Fifty-six studies were eligible for inclusion in the meta-analysis. The result shows that the Ala allele of this polymorphism was associated with increased WMD in mean BMI (WMD = 0.29, 95% CI 0.10-0.48, p = 0.003). The Ala carriers were associated with increased WMD in mean BMI values in both genders and in the Caucasian subgroup. The associations were seen among people with higher levels of BMI (BMI ≥35). Message: The Ala allele of the PPARγ Pro12Ala polymorphism in healthy adults was associated with increased BMI under a dominant model of inheritance.

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“…This variant has also been shown to be associated with lower levels of serum total and nonhigh-density lipoprotein (non-HDL)-cholesterol in a general population [153], lower low-density lipoprotein (LDL)-cholesterol in T2D patients [154], or higher levels of serum HDL-cholesterol in family-based or population-based studies [155, 156]. however, several studies also show an association of Ala12 allele with higher concentration of low-density lipoprotein (LDL)-cholesterol [68, 157] and lower HDL-cholesterol [70]. Interestingly, Pro12Ala mutation interacts with body size at birth to modulate cholesterol metabolism since an association between increased concentration of serum total, LDL- and non-HDL-cholesterol and Ala12 allele can be found only in those who had birth weights below 3 kilograms [158].…”

Section: Effect On Other Components Of Metabolic Syndromementioning

confidence: 99%

PPARγ2^Pro12Ala Polymorphism and Human Health

2009

PPAR Research

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The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPARγ) is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPARγ have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPARγ, Pro12Ala of PPARγ2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interaction between the PPARγ2 Pro12Ala polymorphism and environmental factors such as the ratio of dietary unsaturated fatty acids to saturated fatty acids and/or between the PPARγ2 Pro12Ala polymorphism and genetic factors such as polymorphic mutations in other genes. In addition, this polymorphic mutation in PPARγ2 is associated with other aspects of human diseases, including cancers, polycystic ovary syndrome, Alzheimer disease and aging. This review will highlight findings from recent studies.

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Association of Pro12Ala polymorphism in the peroxisome proliferator–activated receptor γ2 gene with small dense low-density lipoprotein in the general population

Cited by 20 publications

References 28 publications

PPARγ2 Gene Pro12Ala and PPARα Gene Leu162Val Single Nucleotide Polymorphisms Interact with Dietary Intake of Fat in Determination of Plasma Lipid Concentrations

PPARγ2 Gene Pro12Ala and PPARα Gene Leu162Val Single Nucleotide Polymorphisms Interact with Dietary Intake of Fat in Determination of Plasma Lipid Concentrations

Obesity and Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor-Gamma Gene in Healthy Adults: A Systematic Review and Meta-Analysis

PPARγ2^Pro12Ala Polymorphism and Human Health

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Association of Pro12Ala polymorphism in the peroxisome proliferator–activated receptor γ2 gene with small dense low-density lipoprotein in the general population

Cited by 20 publications

References 28 publications

PPARγ2 Gene Pro12Ala and PPARα Gene Leu162Val Single Nucleotide Polymorphisms Interact with Dietary Intake of Fat in Determination of Plasma Lipid Concentrations

PPARγ2 Gene Pro12Ala and PPARα Gene Leu162Val Single Nucleotide Polymorphisms Interact with Dietary Intake of Fat in Determination of Plasma Lipid Concentrations

Obesity and Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor-Gamma Gene in Healthy Adults: A Systematic Review and Meta-Analysis

PPARγ2Pro12Ala Polymorphism and Human Health

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PPARγ2^Pro12Ala Polymorphism and Human Health