| BackgroundMetabolic syndrome (MetS) is a multifactorial disorder characterized by central obesity, dyslipidemia, hypertension, hyperglycemia and insulin resistance. It can lead to a variety of cardiovascular damages including atherosclerosis and structural and functional changes of the heart. The pathogenesis of MetS is very complex. Environmental factors play a significant role in its occurrence while the role of genetic factors has also been recognized. Studies have shown that lots of single nucleotide polymorphisms (SNP) in genes were associated with MetS occurrence and progression.Activin receptor-like kinase7(ALK7) is a newly found type Ⅰ receptor for TGF-β superfamily, and has been demonstrated to play an important role in the maintenance of metabolic homeostasis recently. By binding to type Ⅱ receptors, ALK7activates downstream Smad signaling and participates in the regulation of cell proliferation and apoptosis. It has been found that, by regulating the apoptosis and proliferation of pancreatic (3-cells and fat cells, ALK7is involved in the development of insulin resistance and obesity, and causes MetS phenotype in mice models. Given the important role of ALK7, whether ALK7gene single nucleotide polymorphisms are associated with MetS susceptibility and play a role in its related cardiovascular damages needs to be studied. ObjectiveUsing case-control study to determine the association between SNPs in ALK7gene with MetS incidence and cardiovascular remodeling in the sample population:1. To genotype the ALK7gene SNPs by PCR direct sequencing method in Chinese Han population residing in Shandong Province;2. To investigate the genotype distribution of ALK7gene polymorphisms in Chinese Han population residing in Shandong Province and explore the association between ALK7gene polymorphisms with MetS incidence;3. To explore the association between ALK7gene polymorphisms with MetS components’parameters;4. To explore the association between ALK7gene polymorphisms with carotid atherosclerosis;5. To explore the association between ALK7gene polymorphisms with left ventricular structure and function.Methods1. A total of182MetS cases and169normal controls were collected. Height, weight, waist (WC) and hip circumferences and blood pressure (BP) were measured. Body mass index (BMI) and waist-to-hip ratio (WHR) were then calculated. Ultrasonography of the carotid arteries and the heart was performed. Intima-media thickness (IMT), the ratio of E/A, the ratio of EVA’, left ventricular mass index (LVMI) and E/E’were obtained or calculated.2. Peripheral blood of all participants was collected in the morning after fasting for12-14hours overnight. Levels of triglycerides (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), fasting blood glucose (FBG) and insulin (FINS) were determined. Insulin resistance (HOMA-IR) was assessed. Genomic DNA was extracted, and PCR direct sequencing method was used to genotype the SNPs in exon3, exon4and their nearby regions of ALK7gene.3. Genotype and allele frequencies of ALK7SNP in cases and controls were calculated. Hardy-Weinberg equilibrium was tested. Using a recessive model, genotype distribution was analyzed by X2test. Logistic regression analysis was performed to investigate the association of SNP with MetS phenotype. The association between genotypes and continuous variables was assessed by t test or analysis of covariance. To verify the existence of gender-specificity, stratified analysis of males and females were conducted.Results1. PCR direct sequencing showed that there was an rs13010956polymorphism near exon3of ALK7gene in Chinese Han population residing in Shandong Province. This polymorphism was located in intron3, and its distribution in cases and controls was in Hardy-Weinberg equilibrium.2. Statistical analysis in total population:The difference of genotype distribution of rs13010956between cases and controls was not statistically significant (P>0.05). This polymorphism was not associated with MetS incidence either (P>0.05). However, rs13010956was found to be associated with systolic hypertension (P=0.021). No significant correlation was observed between rs13010956and carotid atherosclerosis indicator IMT (P>0.05). After control of BMI, BP, FBG and TG, rs13010956was found to be significantly associated with left ventricular remodeling indicator LVMI (P=0.043).3. Stratified analysis of males and females:In the female population, the difference of genotype distribution of rs13010956between cases and controls was statistically significant (P=0.009), and rs13010956polymorphism was also found to be significantly associated with MetS incidence (OR=6.949,95%CI:1.451-33.286, P=0.015). However, no above association was observed in the male population (P>0.05for all).4. Further analysis showed that rs13010956was associated with systolic and diastolic blood pressures (P<0.001and P=0.001) in females. Moreover, rs13010956was also found to be significantly associated with mean IMT in the female population (P=0.036). After control of BMI, BP, FBG and TG, the association of rs13010956with mean IMT disappeared (P>0.05) but rs13010956was found to be significantly associated with LVMI (P=0.045). No association of rs13010956polymorphism with clinical parameters was found in males (P>0.05for all).Conclusions1. An rs13010956polymorphism of ALK7gene existed in Chinese Han population residing in Shandong Province. This polymorphism was not associated with MetS incidence in total or male population, but it significantly increased the risk to develop MetS for females.2. In total and female populations, ALK7gene rs13010956polymorphism was found to be significantly associated with hypertension. What’s more, it also showed that rs13010956could affect LVMI independently of obesity, blood pressure, blood glucose and lipids. All these results suggest that rs13010956play a potential role in the progress of heart failure especially in diastolic heart failure.3. There was an association of ALK7gene rs13010956polymorphism with carotid atherosclerosis in females. However, this association disappeared after control of obesity, blood pressure, blood glucose and lipids, suggesting that rs13010956might exert its effect on carotid atherosclerosis just through these parameters. BackgroundSix-transmembrane protein of prostate2(STAMP2), a linker between inflammatory signaling pathways and glucose/lipid metabolism, was reported to play an important role in the maintenance of systemic metabolic homeostasis in animal models and be associated with obesity and insulin resistance in human. Given the important role of STAMP2, whether STAMP2gene single nucleotide polymorphisms (SNPs) are associated with MetS susceptibility and MetS components needs to be further explored.ObjectiveUsing case-control study to determine the association between SNPs in STAMP2gene with MetS incidence and its components in the sample population:1. To genotype the STAMP2gene SNPs by PCR-RFLP method in Han Chinese population residing in Shandong Province;2. To investigate the genotype distribution of STAMP2gene polymorphisms in Han Chinese population residing in Shandong Province and explore the association between STAMP2gene polymorphisms with MetS incidence;3. To explore the association between STAMP2gene polymorphisms with MetS components. MethodsA case-control study enrolled350Han Chinese subjects in two groups:182MetS patients and168control subjects. The clinical and biochemical characteristics were determined. Three single nucleotide polymorphisms (SNPs), rs1981529, rs12386756and rs10263111in STAMP2gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association of STAMP2gene polymorphisms with MetS phenotype and MetS components was analyzed.ResultsSNPs rs1981529and rs10263111were found to be significantly associated with MetS phenotype in male population (P=0.014and0.025). Moreover, SNP rs1981529was found to be associated with high density lipoprotein-cholesterol in male cases and with body mass index in female cases (P=0.014and0.049). SNP rs10263111was found to be associated with both waist circumference and diastolic blood pressure in total cases (P=0.044and0.033). Haplotype analysis yielded significant association of STAMP2gene with MetS in total (global P=0.0109) and male population (global P=0.0004).ConclusionsOur findings revealed that STAMP2gene polymorphisms were significantly associated with MetS phenotype and its risk components, and proved that STAMP2gene polymorphisms were risk factors for MetS in male Han Chinese population. |
PDF Full Text Request