Effects of recent alcohol intake on high density lipoprotein accepting properties and their interactions with liver cells

HDL-subfraction was studied in blood serum of drinkers after alcohol intake and control group of men-nondrinkers. Blood serum incubation with fibroblasts culture did not indicate principal differences between drinkers and nondrinkers both with normolipemia and hyperalphacholesterolemia. Increase of HDL2 and decrease of HDL3-subfraction were observed. Incubation of the same species with hepatoma cells culture (Hep G-2) demonstrated significant differences between normolipemia and hyperalphacholesterolemia. The reduction of HDL2 subfraction level and increase of HDL3 have been found in nondrinkers with normolipemia. The raise of HDL2 was demonstrated in hyperalphacholesterolemia (due to HDL2b and HDL2a in drinkers and HDL2a in nondrinkers). Besides, in several samples of normolipidemic blood serum taken after alcohol abuse the changes of HDL-subfractions were identical to those receiving in hyperalphacholesterolemia. It is postulated that one of the mechanisms of the alcoholic hyperalphacholesterolemia development is the decline of the transfer rate of cholesterol ethers to the liver and accumulation of HDL2 particles in total HDL pool.     

PPAR-gamma2 Pro12Ala polymorphism in the population of obese and non-obese men of the city of Wroclaw

INTRODUCTION: The aim of this study was to examine the association of Pro12Ala PPARgamma2 polymorphism with anthropometric and biochemical parameters defining the risk for the development of metabolic syndrome in a healthy population of men. MATERIAL AND METHODS: The study group consisted of 176 healthy men, aged 25-65 years (average 54.16 years). Polymorphisms of the PPAR-g gene (Pro12Ala, Ala12Ala, Pro12Pro) were explored using the PCR-RFLP method. Plasma glucose, insulin, total cholesterol, LDL, HDL and TG were measured using commercially available kits. RESULTS: The genotypic distribution of the Pro12Ala polymorphism was as follows: Pro/Ala 69.8% (n = 123), Ala/Ala 28.4% (n = 50) and Pro/Pro 1.8% (n = 3). The Pro12Ala and Ala12Ala subjects did not differ in any of the measured variables. The non-obese (BMI < 30 kg/m(2), n = 117) and obese subpopulations (BMI > 30 kg/m(2), n = 56) did not significantly differ in the distribution of the genotypes. In the nonobese subpopulation, the homozygous Ala12 carriers (n = 38, 32.4%) had higher systolic blood pressure, plasma triglycerides, insulin levels and HOMA-IR. CONCLUSIONS: We conclude that despite the high frequency of the Ala allele at the PPAR-gamma2 gene in our population of Polish men, the Ala12 allele does not appear to improve insulin sensitivity or have an influence on the occurrence of obesity. It remains to be explained by larger studies if this polymorphism carries any risk of the development of metabolic abnormalities in non-obese men.     

Associations of alcohol consumption with blood pressure and serum lipids in Japanese female smokers and nonsmokers

Background: Alcohol intake and smoking have been reported to influence atherosclerotic progression.Objective: The purpose of this study was to determine whether the associations of alcohol intake with blood pressure (BP) and serum lipid concentrations are modified by smoking in Japanese women.Methods: Eligible subjects were healthy female Japanese workers aged 35 to <55 years who had received periodic health examinations at workplaces in Yamagata Prefecture in Japan. Subjects were classified as smokers or nonsmokers and subclassified into 3 subgroups based on average daily reported alcohol intake: nondrinkers, light drinkers (<15 g/d), and heavy drinkers (>-15 g/d). The means of each variable (systolic and diastolic BP [SBP and DBP, respectively] and serum concentrations of total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides) were compared among the 2 groups of smoking history and 3 subgroups of alcohol intake after adjusting for age and body mass index.Results: A total of 16,805 healthy women were enrolled (14,695 nonsmokers, 2110 smokers). In smokers, SBP was significantly higher in heavy drinkers than in nondrinkers, and DBP was significantly higher in light drinkers and heavy drinkers than in nondrinkers (all, P < 0.01). In nonsmokers, SBP was not significantly higher in light drinkers and heavy drinkers versus nondrinkers, and the difference in DBP between heavy drinkers and nondrinkers was significant (P < 0.01), but that between light drinkers and nondrinkers was not. In smokers but not in nonsmokers, serum TC concentration was significantly lower in heavy drinkers than in nondrinkers. In smokers and nonsmokers, LDL-C was significantly lower in light and heavy drinkers than in nondrinkers (all, P < 0.01), and serum HDL-C was significantly higher in light and heavy drinkers than in nondrinkers (all, P < 0.01). The differences in mean LDL-C between light and heavy drinkers versus nondrinkers were numerically greater in smokers than in nonsmokers.Conclusion: In this sample of women in Japan, serum LDL-C concentration was significantly lower in drinkers than in nondrinkers, and smoking might increase this association between alcohol intake and lowered LDL-C.     

Differential effects of the C1431T and Pro12Ala PPARgamma gene variants on plasma lipids and diabetes risk in an Asian population

We investigated the association of C1431T and Pro12Ala polymorphisms at the peroxisome proliferator-activated receptor gamma (PPARgamma) locus with plasma lipids and insulin resistance-related variables, according to diabetes status, in a large and representative Asian population from Singapore consisting of 2,730 Chinese, 740 Malays, and 568 Indians. Moreover, we estimated the diabetes risk and examined gene-nutrient interactions between these variants and the ratio of polyunsaturated fatty acid to saturated fat (SFA) in determining body mass index (BMI) and fasting insulin. We found differential effects of these gene variants. The Pro12Ala polymorphism was more associated with plasma lipids and fasting glucose concentrations, whereas the C1431T polymorphism was related to the risk of diabetes. Carriers of the 12Ala allele had higher HDL-cholesterol than did Pro12Pro homozygotes (P < 0.05), and the effect of the 12Ala allele on fasting glucose was modified by diabetes status (P < 0.001). After controlling for confounders, carriers of the T allele had decreased risk of diabetes compared with CC homozygotes [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.58-0.93; P = 0.011]; this effect was stronger in Indians (OR 0.38, 95% CI 0.15-0.92; P = 0.032). For both polymorphisms, normal subjects carrying the less prevalent allele had higher BMI (P < 0.05). The PUFA/SFA did not modify the effect of these polymorphisms on BMI or insulin.     

Interaction between PPARgamma2 variants and gender on the modulation of body weight

Conflicting results have been reported regarding the effect of the peroxisome proliferator-activated receptor-gamma-2 (PPARgamma2) Pro12Ala polymorphism, (singly or in combination with the silent C1431T polymorphism) on BMI. Gender-based dimorphism has been evidenced for genes that affect BMI, but few and conflicting data are available regarding PPARgamma2. We sought to investigate whether the Pro12Ala interacts with gender in modulating BMI in 566 nondiabetic unrelated white subjects (men:women = 211:355, age 36.59 +/- 11.85; BMI 25.36 +/- 4.53). In the whole study population, BMI, fasting glucose and insulin levels, and lipid profile were similar in Ala12 carriers (i.e., XA) and Pro/Pro homozygous subjects. Among the men, but not among the women, X/Ala individuals showed higher BMI (25.9 +/- 3.6 vs. 28.2 +/- 4.9, P = 0.006) and risk of obesity (odds ratio = 2.85, 95% confidence interval = 1.07-7.62). A significant gene-gender interaction in modulating BMI was observed (P = 0.039). Among the men, but not among the women, those carrying Ala-T haplotype (i.e., containing both Ala12 and T1431 variants) showed the highest BMI (haplo-score = 3.72, P = 0.0014). Our data indicate that in whites from Italy the PPARgamma2 Pro12Ala polymorphism interacts with gender in modulating BMI, thereby replicating some, but not all, earlier data obtained in different populations. Whether the PPARgamma2-gender interaction is a general phenomenon across different populations, is still an open question, the answer to which requires additional, specifically designed, studies.     

PPARgamma2 Pro12Ala polymorphism in relation to free fatty acids concentration and composition in lean healthy Czech individuals with and without family history of diabetes type 2

Free fatty acids (FFAs) are natural ligands of the PPARgamma2 receptor. FFA plasma concentration and composition may represent one of the factors accounting for high heterogeneity of conclusions concerning the effect of the Pro12Ala on BMI, insulin sensitivity or diabetes type 2 (DM2) susceptibility. Our objective was to investigate the relation and possible interactions between the Pro12Ala polymorphism and FFA status, metabolic markers, and body composition in 324 lean nondiabetic subjects (M/F: 99/225; age 32+/-11 years; BMI 23.9+/-4.0 kg/m(2)) with and without family history of DM2. Family history of DM2 was associated with lower % PUFA and slightly higher % MUFA. The presence of Pro12Ala polymorphism was not associated with fasting plasma FFA concentration or composition, anthropometric or metabolic markers of glucose and lipid metabolism in tested population. However, the interaction of carriership status with FFA levels influenced the basal glucose levels, insulin sensitivity and disposition indices, triglycerides, HDL-cholesterol and leptin levels, especially in women. The metabolic effects of 12Ala carriership were influenced by FFA levels - the beneficial role of 12Ala was seen only in the presence of low concentration of plasma FFA. Surprisingly, a high PUFA/SFA ratio was associated with lower insulin sensitivity, the protective effect of 12Ala allele was apparent in subjects with family history of DM2. On the basis of our findings and published data we recommend the genotyping of diabetic patients for Pro12Ala polymorphism of the PPARgamma2 gene before treatment with thiazolidinediones and education of subjects regarding diet and physical activity, which modulate metabolic outcomes.     

Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma is associated with increased leptin levels in women with type-2 diabetes mellitus

OBJECTIVE: To analyze the relationship between the peroxisome proliferator-activated receptor-gamma (PPARgamma2) Pro12Ala variant and type-2 diabetes mellitus and its correlation with some cytokine determinants of insulin resistance such as tumor necrosis factor (TNF)-alpha and leptin. METHODS: The PPARgamma2 Pro12Ala genetic polymorphism was studied in 167 type-2 diabetic patients and 63 healthy controls. Serum leptin and plasma-soluble TNF-R2 were measured. RESULTS: Women carriers of the Pro12Ala mutation exhibited higher leptin levels than women non-carriers (median 31.4 vs. 17.5 ng/ml; p < 0.005). sTNF-R2 levels did not show differences between the two genotypes. Analysis by the multiple linear regression model of leptin-body mass index controlled by the PPARgamma2 genotype showed that leptin levels were determined by the Pro12Ala mutation in type-2 diabetic women but not in men. CONCLUSIONS: PPARgamma2 seems to be implicated in leptin homeostasis in type-2 diabetic women.     

Interaction of PPARG Pro12Ala with dietary fat influences plasma lipids in subjects at cardiometabolic risk

The PPARγ2 gene single nucleotide polymorphism (SNP) Pro12Ala has shown variable association with metabolic syndrome traits in healthy subjects. The RISCK Study investigated the effect of interaction between genotype and the ratio of polyunsaturated:saturated (P:S) fatty acid intake on plasma lipids in 367 white subjects (ages 30-70 years) at increased cardiometabolic risk. Interaction was determined after habitual diet at recruitment, at baseline after a 4-week high-SFA (HS) diet, and after a 24-week reference (HS), high-MUFA (HM), or low-fat (LF) diet. At recruitment, there were no significant associations between genotype and plasma lipids; however, P:S × genotype interaction influenced plasma total cholesterol (TC) (P = 0.02), LDL-cholesterol (LDL-C) (P = 0.002), and triglyceride (TG) (P = 0.02) concentrations. At P:S ratio ≤ 0.33, mean TC and LDL-C concentrations in Ala12 allele carriers were significantly higher than in noncarriers (respectively, P = 0.003; P = 0.0001). Significant trends in reduction of plasma TC (P = 0.02) and TG (P = 0.002) concentrations occurred with increasing P:S (respectively, ≤0.33 to >0.65; 0.34 to >0.65) in Ala12 allele carriers. There were no significant differences between carriers and noncarriers after the 4-week HS diet or 24-week interventions. Plasma TC and TG concentrations in PPARG Ala12 allele carriers decrease as P:S increases, but they are not dependent on a reduction in SFA intake.     

Fetal and maternal peroxisome proliferator-activated receptor gamma2 Pro12Ala does not influence birth weight

The association between the peroxisome proliferator-activated receptor (PPAR)gamma2 Pro12Ala polymorphism and insulin resistance is reported to depend on low birth weight. Low birth weight itself has been linked to type 2 diabetes and cardiovascular diseases in adulthood. We assessed whether the PPARgamma2 Pro12Ala polymorphism determines body size at birth and whether metabolic differences between the genotypes are already detectable in the newborn. This study was conducted at the obstetrics department of the Charité, Berlin, Germany. One thousand nine hundred thirty white woman/child pairs were consecutively included and genotyped. The newborn's weight, length, and head circumference were measured. Total glycated hemoglobin in blood served as a surrogate of fetal insulin resistance and glucose use. We found that neither the fetal nor the maternal Pro12Ala genotype determined body size or total glycated hemoglobin at birth. The results suggest that the PPARgamma2 Pro12Ala polymorphism is not relevant for intrauterine growth. Previously reported effects of PPARgamma2 Pro12Ala on insulin resistance seem to arise later in life.     

Evidence for greater oxidative substrate flexibility in male carriers of the Pro 12 Ala polymorphism in PPARgamma2.

The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma2 (PPARgamma2) gene is associated with reduced type 2 diabetes risk and increased insulin sensitivity. It is possible that the oxidative shift from lipid to glucose as a fuel is more efficient in Ala allele carriers. To test this hypothesis, we examined carbohydrate and lipid oxidation by indirect calorimetry in lean, glucose tolerant subjects with (X/Ala, n = 25) and without the Pro12Ala polymorphism (Pro/Pro, n = 73) basally and after insulin stimulation during a 2-hour eugylcaemic hyperinsulinaemic clamp. Insulin sensitivity was non-significantly greater in X/Ala (0.13 +/- 0.01 micromol/kg/min/pM) than in Pro/Pro (0.12 +/- 0.01 micromol/kg/min/pM, p = 0.27). Basally, there were no lipid nor carbohydrate oxidation differences between the groups. Interestingly, the decrease in lipid oxidation during insulin stimulation was significantly greater in male X/Ala (- 0.51 +/- 0.06 mg/kg/min) than in male Pro/Pro (- 0.35 +/- 0.04 mg/kg/min, p = 0.03). No difference was observed in females. Analogously, the change in carbohydrate oxidation in male X/Ala (1.34 +/- 0.2 mg/kg/min) was significantly greater than in male Pro/Pro (1.03 +/- 0.12 mg/kg/min, p = 0.05). The respiratory quotient increased more, but not significantly more, in male X/Ala (0.11 +/- 0.01) than in male Pro/Pro subjects (0.08 +/- 0.01, p = 0.08) but similarly in females. These results indicate that the mechanism by which the Ala allele improves insulin sensitivity might involve enhanced suppression of lipid oxidation permitting more efficient (predominantly non-oxidative) glucose disposal. It is unclear why this could be demonstrated only in males, although gender differences in substrate oxidation are well documented.     

Association between PPARγ2 Pro12Ala polymorphism and myocardial infarction and obesity in Han Chinese in Hohhot, China

Activation of the peroxisome proliferator-activated receptor g (PPARg) improves insulin sensitivity and inhibits atherosclerosis. Whether PPARg2 Pro12Ala polymorphism affects myocardial infarction is not clearly understood. We investigated a possible association of PPARg2 Pro12Ala polymorphism with obesity and myocardial infarction in Han Chinese in Hohhot, Inner Mongolia, China. We included 121 subjects with myocardial infarction and 137 healthy controls in our study. Triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were measured. The following information was recorded for each subject: age, gender, body height, body weight, systolic blood pressure, and diastolic blood pressure; the body mass index was calculated. PCR-RFLP was used to examine Pro12Ala polymorphism. There were significant differences in clinical characteristics between myocardial infarction patients and healthy controls, except for diastolic blood pressure and triglycerides. The PP, PA/AA genotype frequencies were 88.4 and 11.6% in myocardial infarction patients and 95.6 and 4.4% in controls, respectively (P = 0.031). Individuals with the A allele had a significantly higher risk of myocardial infarction. The A allele was not an independent risk factor for obesity. We conclude that PPARg2 Pro12Ala polymorphisms are associated with increased risk for myocardial infarction in Han Chinese in Hohhot.     

Gene–diet-related factors of hyperglycaemia in postmenopausal women

As ageing and increased body fat are the signs of insulin resistance, we have studied whether the presence of Pro12Ala and C1431T of peroxisome proliferator-activated receptor gamma 2 gene and Trp64Arg of beta 3-adrenergic receptor gene may predispose to the hyperglycaemia development in postmenopausal women, who have never undergone hypoglycaemic treatment. The distributions of selected allele and genotype frequencies were determined by the PCR–RFLP method in normo- and hyperglycaemic, who have never been diagnosed and treated for diabetes mellitus were measured. The amount of body fat and lean body mass (LBM) were assessed by the bioimpedance method and nutritional habits by 7-day dietary recall. There were no differences between the distribution of genotypes and the allele frequencies of the Pro12Ala, C1431T and Trp64Arg polymorphisms in normo- and hyperglycaemic women. Hyperglycaemic women were characterized by visceral obesity, hypertension, higher serum insulin and triglycerides, higher intake of fat and lower consumption of complex carbohydrates and B vitamins. Normoglycaemic women with Pro12Pro polymorphism acquired higher energy from dietary fat (p?<?0.0276) and lower energy from carbohydrates (p?<?0.0480) than normoglycaemic Ala12 carriers. Subjects with Pro12Pro polymorphism and LBM >?58% of total body mass or with Trp64Trp and normal triglycerides have higher chance of normoglycaemia. Genotyping for Pro12Ala and Trp64Arg polymorphism in postmenopausal women may have the clinical benefit of predicting hyperglycaemia, thereby contributing to the prevention of diabetes mellitus development in the future. However, not only the genetic background but also the dietary habits (intake of fat, carbohydrates and B vitamins) determine the risk of hyperglycaemia.     

Polymorphisms in genes involved in the inflammatory response and interaction with NSAID use or smoking in relation to lung cancer risk in a prospective study

Lung cancer risk was investigated in relation to single nucleotide polymorphisms in genes involved in the inflammatory response. The aim was to see if polymorphisms modifying the inflammatory response are associated with risk of lung cancer and if there were interactions between the same polymorphism and factors, which modify an inflammatory response, such as smoking status, duration, and intensity, and use of NSAID. The functional SNPs IL-1B T-31C, IL6 G-174C, IL8 T-251A, IL10 C-592T, COX2 C8473T, COX2 A-1195G and PPARgamma2 Pro(12)Ala were included. A case-cohort study including 428 lung cancer cases and a sub-cohort of 800 persons was nested within a population-based prospective study of 57,053 individuals. Variant allele carriers of IL-1B T-31C were at increased risk of lung cancer (IRR=1.51, 95% CI=1.08-2.12). There was interaction between the polymorphism COX-2 T8473C and smoking status. Thus, non-smoking variant allele carriers were at 5.75-fold (95% CI=1.25-26.43) higher risk of lung cancer than for homozygous wild type allele carriers. Lung cancer risk was similar for all genotype carriers among past and current smokers. There were, however, very few non-smoking lung cancer cases. There was interaction between IL-1B T-31C, COX-2 A-1195G and PPARgamma2 Pro(12)Ala and NSAID use in relation to lung cancer risk. For the two latter, NSAID use was only associated with a lower cancer risk among homozygous wild type allele carriers. p for interaction was 3 x 10(-6) for COX-2 A-1195G and 9 x 10(-5) for PPARgamma2 Pro(12)Ala. The results suggest that NSAID use may modify risk of lung cancer differently depending on the genotype.     

The lipoprotein lipase S447X polymorphism and plasma lipids: interactions with APOE polymorphisms, smoking, and alcohol consumption

We studied 4,058 subjects from a representative sample of the Singapore population 1) to determine the association between the S447X polymorphism at the LPL locus and serum lipid concentration in Chinese, Malays, and Asian Indians living in Singapore and 2) to explore any interactions with apolipoprotein E (APOE) genotype, exercise, obesity, cigarette smoking, and alcohol intake. Information on obesity, lifestyle factors (including smoking, alcohol consumption, and exercise frequency), glucose tolerance, and fasting lipids was obtained. Male and female carriers of the X447 allele had lower serum triglyceride concentrations and higher HDL cholesterol (HDL-C) concentrations. The association between the X447 allele and serum HDL-C concentration was modulated by APOE genotype in males and cigarette smoking and alcohol intake in females. The effect of the X447 allele was greatest in men who carried the E4 allele and women who smoked or consumed alcohol. The X447 allele at the LPL locus is common and associated with a less atherogenic lipid profile in Asian populations. Interactions with APOE genotype, cigarette smoking, and alcohol intake reinforce the importance of examining genetic associations, such as this one, in the context of the population of interest.     

Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with polycystic ovary syndrome: a meta-analysis

The association between Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma (PPAR) and polycystic ovary syndrome (PCOS) has been investigated in several studies, whereas results were often incompatible. We conducted a meta-analysis to evaluate the association of Pro12Ala polymorphism in PPAR with PCOS susceptibility. A meta-analysis was performed on the published studies before November, 2011. Meta-analysis was performed for genotypes CG versus CC, CG+GG versus CC and G allele versus C allele in a fixed effect model. The combined odds ratio (OR) with 95?% confidence interval (95?% CI) was calculated to estimate the strength of the association. A total of 13 studies including 1,598 cases and 1,881 controls were enrolled. Ultimately, sensitivity analysis demonstrated that, in total, there was no significant association between Pro12Ala polymorphism and PCOS in the contrast of G allele versus C allele OR?=?0.84 (95?% CI 0.69-1.04) and in Europeans, no significant association in the comparison of G allele versus C allele (OR?=?0.84, 95?% CI 0.67-1.06) was also indicated. In summary, according to the results of our meta-analysis, strictly, the Pro12Ala polymorphism did not significantly associate with PCOS, though the protective trend of G allele existed.     

Dietary polyunsaturated fatty acids and the Pro12Ala polymorphisms of PPARG regulate serum lipids through divergent pathways: a randomized crossover clinical trial

Human and animal studies suggest an interaction between the Pro12Ala polymorphism of PPARG and dietary fat. In this randomized crossover clinical trial, we investigated whether subjects with the Pro12Pro and Ala12Ala genotypes of PPARG respond differently to a diet supplemented with high saturated (SAFA) or polyunsaturated fatty acid (PUFA).We recruited non-diabetic men from a population-based METSIM study (including 10,197 men) to obtain men with the Ala12Ala and the Pro12Pro genotypes matched for age and body mass index. Seventeen men with the Pro12Pro genotype and 14 with the Ala12Ala genotype were randomized to both a PUFA diet and a SAFA diet for 8 weeks in a crossover setting. Serum lipids and adipose tissue mRNA expression were measured during the diet intervention. At baseline, subjects with the Ala12Ala genotype had higher levels of HDL cholesterol and lower levels of LDL cholesterol, total triglycerides, and apolipoprotein B compared to those subjects with the Pro12Pro genotype (P < 0.05, FDR < 0.1). The Ala12Ala genotype also associated with higher mRNA expression of PPARG2, LPIN1, and SREBP-1c compared to participants with the Pro12Pro genotype (FDR < 0.001). On the other hand, PUFA diet resulted in lower levels of fasting glucose, total cholesterol, total triglycerides, and apolipoprotein B (P < 0.05, FDR < 0.1) but did not affect PPARG2 mRNA expression in adipose tissue. We conclude that individuals with the Pro12Pro genotype, with higher triglyceride levels at baseline, are more likely to benefit from the PUFA diet. However, the beneficial effects of dietary PUFA and the Ala12Ala genotype of PPARG on serum lipids are mediated through divergent mechanisms.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-015-0493-z) contains supplementary material, which is available to authorized users.     

Association of peroxisome proliferator-activated receptor γ Pro12Ala gene polymorphism with type 2 diabetic nephropathy risk in Caucasian population

Abstract

Association of peroxisome proliferator-activated receptor gamma (PPARγ) Pro12Ala gene polymorphism with type 2 diabetic nephropathy (T2DN) risk in Caucasians is still not clear. This investigation was conducted to assess if there was an association between the PPARγ Pro12Ala gene polymorphism and T2DN risk in Caucasians using meta-analysis. The relevant literatures were identified from PubMed, and Cochrane Library on 10 October 2013, and eligible studies were included and synthesized. Six reports including eight studies were recruited into this meta-analysis for the association of the PPARγ Pro12Ala gene polymorphism with T2DN risk in Caucasians. The Pro/Pro genotype was shown to be associated with T2DN risk in Caucasians. However, the Ala/Ala genotype and Ala allele were not associated with T2DN risk in Caucasians. In the sensitivity analysis, according to the control source from hospital, the control source from population, the genotyping methods using PCR-RFLP, Taqman, sample size of case <100, the association of the PPARγ Pro12Ala gene polymorphism with T2DN risk was similar to those in non-sensitivity analysis. In conclusion, the PPARγ Pro/Pro genotype was associated with T2DN risk in Caucasians, but the Ala/Ala genotype and Ala allele not. However, additional studies are required to firmly establish a correlation between the PPARγ Pro12Ala gene polymorphism and T2DN risk in Caucasians.