Effects of Pro12Ala polymorphism in peroxisome proliferator-activated receptor-γ2 gene on metabolic syndrome risk: A meta-analysis

Background

Associations between peroxisome proliferator-activated receptor γ2 (PPARγ2) gene polymorphism and metabolic syndrome risk remained controversial and ambiguous. Thus, we performed a meta-analysis to assess the association between Pro12Ala polymorphism in PPARγ2 gene and metabolic syndrome susceptibility.

Methods

An electronic literature search was conducted on Medline, OVID, Cochrane Library database, and the China National Knowledge Internet up to March 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association in the fixed or random effects model.

Results

Ten studies involving a total of 4456 cases and 10343 controls were included in this meta-analysis. No statistical evidence of association was found between Pro12Ala polymorphism and metabolic syndrome risk in all genetic models (homozygote model: OR = 0.83, 95% CI = 0.62–1.12; heterozygote model: OR = 1.04, 95% CI = 0.94–1.14; dominant model: OR = 1.02, 95% CI = 0.93–1.12; recessive model: OR = 0.83, 95% CI = 0.62–1.11). No statistical evidence of significant association was observed when stratified by ethnicity, definition of metabolic syndrome, source of control groups and quality score of the selected articles. All in all, the results did not support a major role of the Pro12Ala variant of the PPARγ2 gene in metabolic syndrome risk.

Conclusions

This meta-analysis suggested that the effect of Pro12Ala polymorphism in PPARγ2 gene may not be related to metabolic syndrome as an entity. However, Pro12Ala may affect the single component of metabolic syndrome. A large, well designed study is required to more adequately assess the role for Pro12Ala polymorphism on metabolic syndrome.     

Association between the ghrelin Leu72Met polymorphism and type 2 diabetes risk: A meta-analysis

Aims

Data on the association between the ghrelin Leu72Met polymorphism and type 2 diabetes are conflicting. A meta-analysis was performed on this topic.

Methods

We searched for case–control studies using electronic databases (Medline and PubMed) and reference lists of studies. Odds ratios (OR) and 95% confidence intervals (CI) assuming dominant, recessive and homozygote comparison genetic models were calculated.

Results

Six case–control studies involving a total of 3417 cases and 3081 controls were included in this meta-analysis. No association was found between the ghrelin Leu72Met polymorphism and type 2 diabetes risk in the overall population in dominant, recessive and homozygote comparison models. However, in subgroup analyses stratified by ethnicity, we found that the risk for type 2 diabetes was decreased in subjects with Met72 + genotypes in Caucasians (OR = 0.79, 95% CI: 0.64–0.98, P_z = 0.030).

Conclusion

The ghrelin Leu72Met polymorphism was protective against type 2 diabetes in Caucasians. Future studies performed in larger sample size are needed to allow a more definitive conclusion.     

Apolipoprotein A5 T-1131C variant and risk for metabolic syndrome in obese adolescents

Background

Apolipoprotein A5 (APOA5) gene variants are associated with increased plasma triglycerides, a risk factor for metabolic syndrome (MS). The goal of the current study was the investigation of the distribution of T-1131C variant among obese adolescents with MS compared with healthy controls.

Subjects and methods

The study included 150 obese adolescents (75 males and 75 females) with MS and 204 age and sex matched normal healthy controls (100 males and 104 females). The mean age of the patients was 15.47 ± 2.54 years, ranged from 17 to 20 years. They were genotyped by polymerase chain reaction–restriction fragment length polymorphism for the mutation (T-1131C).

Results

The blood pressure, triglyceride and HOMA-R levels were significantly higher and HDL-C levels were significantly lower in carrier (TC + CC) compared to non-carrier (TT) MS patients. There was accumulation of − 1131C allele frequency in the MS group (31.33% vs. control group 11.76%), p < 0.001. The genotypes were in Hardy–Weinberg equilibrium both in the patients with metabolic syndrome and in the control subjects. Results of analysis of multiple regression models showed that the ApoA5 − 1131C carriers showed an increased incidence of MS (OR = 1.73, 95% CI: 1.41–2.11).

Conclusions

The present study suggests that the 1131T>C polymorphism is a risk factor for the development of metabolic syndrome in obese adolescents.     

Association of adiponectin (AdipoQ) and sulphonylurea receptor (ABCC8) gene polymorphisms with Type 2 Diabetes in North Indian population of Punjab

In Type 2 Diabetes (T2D), adiponectin (AdipoQ) and sulphonylurea receptor genes (ABCC8) are important targets for candidate gene association studies. The single nucleotide polymorphisms (SNPs) in these genes have been associated with features of the metabolic syndrome across various populations. The present case–control study undertaken in the population of Punjab, evaluates the association of + 45T>G polymorphism in AdipoQ gene; and Exon16-3C>T as well as Exon18C>T polymorphisms in ABCC8 gene with T2D. These SNPs were genotyped in 200 T2D cases and 200 non-diabetic healthy controls using the PCR-RFLP method. The frequency of the minor G-allele for AdipoQ+ 45(T>G) polymorphism was significantly higher in T2D cases (29.0%) than in controls (21.5%) [P = 0.02, OR = 1.49 (1.07–2.04)]. The genetic model analysis revealed that the G-allele cumulatively provides nearly 1.59–1.78 fold increased risk to T2D under the additive (P = 0.009; OR = 1.59, 1.12–2.25 at 95% CI), dominant (TG/GG vs. TT) (P = 0.034, OR = 1.64, 1.04–2.56 at 95% CI) and codominant model (TG vs. TT/GG) (P = 0.014; OR = 1.78, 1.12–2.82 at 95% CI) after adjusting for confounding factors. However, no difference in the distribution of genotype and allele frequencies was observed for both the ABCC8 polymorphisms. The distribution of obesity profiles (BMI, WC and WHR) was also significantly different between cases and controls (P < 0.05). Higher BMI and central obesity were observed to increase the risk of T2D. G-allele of + 45(T>G) polymorphism in the adiponectin gene appears to be associated with increased risk of T2D, but the polymorphisms in sulphonylurea receptor gene do not seem to be associated with T2D in the population of Punjab.     

Association of adiponectin promoter variants with traits and clusters of metabolic syndrome in Arabs: Family-based study

Plasma levels of adiponectin are decreased in type 2 diabetes, obesity and hypertension. Our aim was to use a family-based analysis to identify the genetic variants of the adiponectin (ADIPOQ) gene that are associated with obesity, insulin resistance, dyslipidemia and hypertension, among Arabs. We screened 328 Arabs in one large extended family for single nucleotide polymorphisms (SNPs) in the promoter region of the ADIPOQ gene. Two common SNPs were detected: rs17300539 and rs266729. Evidences of association between traits related to the metabolic syndrome and the SNPs were studied by implementing quantitative genetic association analysis. Results showed that SNP rs266729 was significantly associated with body weight (p-value = 0.001), waist circumference (p-value = 0.037), BMI (p-value = 0.015) and percentage of total body fat (p-value = 0.003). Up to 4.1% of heritability of obesity traits was explained by the rs266729 locus. Further cross-sectional analysis showed that carriers of the G allele had significantly higher values of waist circumference, BMI and percentage of total body fat (p-values 0.014, 0.004 and 0.032, respectively). No association was detected between SNP rs266729 and other clusters of metabolic syndrome or their traits except for HOMA-IR and fasting plasma insulin levels, p-values 0.035 and 0.004, respectively. In contrast, both measured genotype and cross-sectional analysis failed to detect an association between the SNP rs17300539 with traits and clusters of metabolic syndrome. In conclusion, we showed family-based evidence of association of SNP rs266729 at ADIPOQ gene with traits defining obesity in Arab population. This is important for future prediction and prevention of obesity in population where obesity is in an increasing trend.     

The potential role of green tea catechins in the prevention of the metabolic syndrome - A review

The metabolic syndrome (MetS) represents an emerging health burden for governments and health care providers. Particularly relevant for prevention and early management of MetS are lifestyle conditions including physical activity and the diet. It has been shown that green tea, when consumed on a daily basis, supports health. Many of the beneficial effects of green tea are related to its catechin, particularly (−)-epigallocatechin-3-gallate (EGCG), content. There is conclusive evidence from in vitro and animal studies which provide the concepts for underlying functional mechanisms of green tea catechins and their biological actions. An increasing number of human studies have explored the effects of green tea catechins on the major MetS conditions such as obesity, type-2 diabetes and cardiovascular risk factors. This article provides a comprehensive overview of the human studies addressing the potential benefits of green tea catechins on the MetS.The number of human studies in this field is still limited. However, the majority of human epidemiological and intervention studies demonstrate beneficial effects of green tea or green tea extracts, rich in EGCG on weight management, glucose control and cardiovascular risk factors. The optimal dose has not yet been established.The current body of evidence in humans warrants further attention. In particular, well-controlled long-term human studies would help to fully understand the protective effects of green tea catechins on parameters related to the MetS.     

Association between chemerin rs17173608 and vaspin rs2236242 gene polymorphisms and the metabolic syndrome,a preliminary report

Metabolic syndrome (MeS) is associated with increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. There is some evidence indicating that adipokines play a role in the development of MeS. The present study was aimed to investigate the impact of chemerin rs17173608 and vaspin rs2236242 gene polymorphisms with the risk of MeS in a sample of Iranian population.     

Association of VDR-gene variants with factors related to the metabolic syndrome,type 2 diabetes and vitamin D deficiency

The prevalence of metabolic syndrome (MetS) is rising alarmingly in the Saudi Arabian population. This study was conducted to assess the association between vitamin D receptor (VDR) polymorphisms and genetic susceptibility to components of the metabolic syndrome, type 2 diabetes mellitus (T2DM), and vitamin D deficiency in the Saudi Arabian population. Five-hundred-seventy Saudi individuals (285 MetS and 285 controls) were enrolled in this cross-sectional study. TaqI, BsmI, ApaI and FokI single nucleotide polymorphisms (SNPs) of the VDR gene were genotyped. The CT genotype and allele T of BsmI were associated with lower HDL-C levels [OR 0.60 (0.37, 0.96), p = 0.03] and obesity [OR 1.4 (1.0, 1.90), p = 0.04], respectively. The CT genotype and the dominant model CT + TT of BsmI were associated with increased risk of diabetes [OR 1.7 (1.2, 2.4), p = 0.007], and [OR 1.5 (1.1, 2.2), p = 0.01], respectively. On the contrary, the CT and CT + CC genotypes of FokI exhibited an association with a reduced risk of diabetes [OR 0.70 (0.49, 0.99), p = 0.05] and [OR 0.67 (0.48, 0.94), p = 0.02], respectively. The allele C of FokI was associated with lower risk of developing T2DM [OR 0.73 (0.56, 0.95), p = 0.02]. The prevalence of vitamin D deficiency was lower in subjects with the AC genotype of ApaI [OR, 0.34 (0.14, 0.80), p = 0.01]. Components of the MetS such as obesity, low HDL and T2DM were associated with the VDR gene. FokI and BsmI have protective and facilitative effects on the risk for T2DM, while the ApaI genotype was associated with reduced vitamin D deficiency.