Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and risk of preeclampsia: an updated meta-analysis based on 51 studies.

BACKGROUND AND AIMS: The methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism has been considered to be associated with preeclampsia (PE), but the results from previous studies were conflicting. The present study aimed at investigating the frequency of preeclampsia according to the distribution polymorphism using a meta-analysis on the published studies. METHODS: The English and Chinese databases were searched to identify eligible studies published in English before August 2012. Data were extracted using standardized methods. The association was assessed by odds ratio (OR) with 95% confidence intervals (CI). Begg's test was used to measure publication bias. RESULTS: A total of 51 case-control studies containing 6,403 patients and 11,346 controls were involved in this meta-analysis. Significant associations were detected between MTHFR C677T polymorphism and risk of PE in the overall population for TT vs. CC (OR = 1.280, 95% CI: 1.074-1.525), recessive model (OR = 1.264, 95% CI: 1.067-1.303), and dominant genetic model (OR = 1.174, 95% CI: 1.057-1.303); in Caucasian population for dominant model (OR = 1.136, 95% CI: 1.022-1.263), and in East Asia population for TT vs. CC (OR = 2.199, 95% CI: 1.366-3.924) CT vs. CC (OR = 1.453, 95% CI: 1.001-2.109), recessive model (OR = 1.742, 95% CI: 1.202-2.525), and dominant model (OR = 1.783, 95% CI: 1.271-2.501). Conversely, no associations were detected in Latin America, South Asia, and Africa populations. CONCLUSIONS: Results of the meta-analysis suggest that the MTHFR C677T polymorphism was associated with risk of PE in overall, Caucasian, and East Asia populations. Nevertheless, the results for Latino, East Asians, South Asians and Africans should be interpreted with caution due to the small sample size.

Lower ADD1 gene promoter DNA methylation increases the risk of essential hypertension.

The goal of our study is to investigate the contribution of promoter DNA methylation of α-adducin (ADD1) gene to the risk of essential hypertension (EH). Using the bisulphite pyrosequencing technology, DNA methylation levels of five CpG dinucleotides on ADD1 promoter were measured among 33 EH cases and 28 healthy controls. Significantly higher ADD1 DNA methylation levels were observed in the females than in the males (CpG1: P = 0.016; CpG2-5: P = 0.021). A breakdown analysis by gender showed that lower CpG1 methylation was associated with an increased risk of EH in females (adjusted P = 0.042). A much more significant association between lower CpG2-5 methylation levels and the increased risk of EH was found in males (adjusted P = 0.008). CpG1 methylation was inversely correlated with age in females (r = -0.407, P = 0.019) but not in males. ADD1 CpG1 and CpG2-5 methylation levels were significantly lower in post-menopausal (>50 years) women than pre-menopausal (≤50 years) women (CpG1: P = 0.006; CpG2-5: P = 0.034). A significant interaction between CpG1 methylation and age was found in females (CpG1*age: P = 0.029). CpG2-5 methylation was shown as a significant predictor of EH in males [area under curve (AUC) = 0.855, P = 0.001], in contrast that CpG1 methylation was a trend toward indicator in females (AUC = 0.699, P = 0.054). In addition, significant differences were observed between males and females for alanine aminotransferase (ALT, P = 0.001), aspartate aminotransferase (AST, P = 0.005) and uric acid (P<0.001). The concentration of AST was inversely correlated with ADD1 CpG2-5 methylation levels in female controls (r = -0.644, P = 0.024). These observations may bring new hints to elaborate the pathogenesis of EH.

Positive correlation between variants of lipid metabolism­related genes and coronary heart disease.

Four gene variants related to lipid metabolism (including the rs562338 and rs503662 variants of the APOB gene, the rs7767084 variant of the LPA gene and the rs2246942 variant of the LIPA gene) have been shown to be associated with coronary heart disease (CHD). The aim of the present study was to assess their association with CHD in the Han Chinese population and to assess the contribution of these gene variants to CHD. Using the standardized coronary angiography method, we enrolled 290 CHD patients and 193 non-CHD patients as non-CHD controls from Lihuili Hospital (Ningbo, China). In addition, we recruited 330 unrelated healthy volunteers as healthy controls from the Xi Men Community (Ningbo, China). Our results demonstrated that the rs503662 and rs562338 variants of the APOB gene were extremely rare in the Han Chinese population (minor allele frequency <1%). Genotype rs2246942-GG of the LIPA gene was associated with an increased risk of CHD [CHD cases versus healthy controls: P=0.04; odds ratio (OR)=1.63; 95% confidence interval (CI)=1.02-2.60). Genotype rs7767084-CC of the LPA gene was identified as a protective factor against CHD in females (CHD cases versus non-CHD controls: P=0.04, OR=0.21; CHD cases versus healthy controls: P=0.02, OR=0.21). The results of our meta-analysis indicated that rs7767084 was not associated with a high risk of CHD (P=0.83; combined OR=0.93; 95% CI=0.47-1.85). In the present study, two single nucleotide polymorphisms (SNPs) of genes involved in lipid metabolism (rs2246942 and rs7767084) were identified to be significantly associated with CHD in the Han Chinese population. Specifically, rs2246942-GG of the LIPA gene was a risk factor for CHD, while rs7767084-CC of the LPA gene was a protective factor against CHD in females. However, our meta-analysis indicated that rs7767084 is not associated with a higher risk of CHD.