| Background Metabolic syndrome is a special disease state associated with increasing the risk of cardiovascular disease morbidity and mortality.The characteristic of metabolic syndrome is that it combined a variety of metabolic disorders,including obesity,hyperglycemia,hypertension,dyslipidemia,high uric acid,high incidence of fatty liver and hyperinsulinemia.These metabolic disorder is the pathology of cardiovascular disease,cerebrovascular disease,and diabetes mellitus.At present,it is believed that the insulin resistance and hyperinsulinemia caused by obesity,especially the central obesity,may be their common pathological basis.Mitofusin 2(Mfn2)was first found by professor Kuang-Hueih Chen in 1997.It has been widely recognized that overexpression of Mfn2 gene can inhibit the proliferation of VSMCs and promote mitochondrial fusion.Many researches have been found that the single nucleotide polymorphism(SNP)was associated with essential hypertension,dyslipidemia and insulin resistance.Therefore,we hypothesized that the Mfn2 gene SNP may be associated with other symptoms of metabolic syndrome(obesity,hyperuricemia etc.).Objective 1.To evaluate the relationship between the rs17037564 polymorphisms of the Mfn2 gene and obesity and obese hypertension among the northern Han Chinese population,which many provide theoretical basis for early prevention and individualized diagnosis and treatment of obese hypertension.2.To evaluate the association between the rs2336384,rs2295281,rs17037564,rs2236057,rs2236058 and rs3766741 polymorphisms of the Mfn2 gene and hyperuricemia(HUA)among the northern Han Chinese population,which may provide genetic theory for the early risk evaluation of HUA.Methods 1.All individuals in this case-control study were of northern Han Chinese origin.A total of 447 unrelated participants comprising 231 hypertensive patients and 216 normotensive control subjects were recruited.We collected the clinical characteristics and blood samples of all participants.We genotyped the SNP(rs17037564)using the Taq Man assay.The correlations between different genotypes of rs17037564 and obesity and obese hypertension were analyzed by Mantel-Haenszel test.The SPSS 22.0 software was used to perform the statistical analyses.2.All individuals in this case-control study were of northern Han Chinese origin.A total of 750 unrelated participants comprising 250 HUA patients and 500 normouricemia control subjects were recruited.We collected the clinical characteristics and blood samples of all participants.We genotyped the SNPs(rs2336384,rs2295281,s17037564,rs2236057,rs2236058 and rs3766741)using the Taq Man assay.The SPSS 22.0 software was used to perform the statistical analyses.The association between the SNPs of Mfn2 gene and HUA risk was evaluated through univariate analyses,stratification analyses,linkage disequilibrium and haplotype analyses.Results 1.GG+AG genotype of rs17037564 was found to be significantly associated with decreased risk of hypertension(P= 0.02).There was no significant difference in the incidence of obesity in different genotypes of rs17037564(GG+AG vs AA)(P=0.852).Different genotypes of rs17037564(GG+AG vs AA)had significant differences in the prevalence of Obesity-related hypertension(P< 0.001).Considering the effect of rs17037564 on blood pressure,there was still significant association between obesity and hypertension.(P<0.001).2.(1)The genotype and allele frequency distribution of SNP rs2236384,rs2236057 and rs2236058 were statistically different between the HUA cases and control subjects(P<0.05)in the whole population group,male subgroup and female subgroup.(2)Logistic regression analysis was performed after adjustment for the potential covariates.(1)In the whole population group:rs2236057 polymorphism was significantly associated with an increased risk for HUA in Dominant genetic model(OR=1.491,95% CI [1.022-2.175],P=0.038).(2)In male subgroup:the significant association between Mfn2 gene polymorphism and HUA was found in the dominant genetic model of rs2336384(OR=1.784,95% CI [1.080-2.946],P=0.024),the dominant genetic model of rs2236057(OR=1.983,95% CI [1.239-3.176],P=0.004)and the recessive genetic model of rs2236058(OR=0.545,95% CI[0.314-0.947],P= 0.031).(3)In female population group: rs3766741 polymorphism was significantly associated with an increased risk for HUA in both Dominant genetic model(OR=2.532,95% CI [1.166-5.499],P=0.019)and Allele model(OR=3.421,95% CI [1.192-4.917],P=0.014).(3)The 6 genetic models,mentioned in the result(2),were independent risk factors of an increased risk for HUA,and have no significant interaction with essential hypertension,blood urea nitrogen and creatinine.(4)The six polymorphisms of the Mfn2 gene were in tight linkage disequilibrium with each other.Five haplotypes were detected in the haplotype analyses.The A-T-A-G-G-C(rs2336384,rs2295281,rs17037564,rs2236057,rs2236058,rs3766741)haplotype was the only one risk haplotype(P=0.039)found in the chi-square test.Logistic regression analysis didn’t found association with HUA risk in this case-control study.Conclusion 1.Mfn2 gene polymorphism(rs17037564)may associate with hypertension.There was no significant difference in the incidence of obesity in different genotypes of rs17037564.Compared with AA genotype of rs17037564,GG+AG genotype is a protective factor for hypertensive,and it also plays a similar role in the obesity-related hypertension.2.The rs2336384,rs2236057,rs2236058 and rs3766741 polymorphisms of the Mfn2 gene were associated with hyperuricemia(HUA)risk in the northern Han Chinese population.The AA+AG genotype of rs2236057 was observed to be a risk factor for HUA,which was more pronounced in male subgroup.The man with CC+CA genotype of rs2236384 and the woman with G allele of rs3766741 have an increased risk for HUA.In male subgroup GG genotype of rs2236058 can reduce the risk for HUA.The 6 genetic models of rs2336384,rs2236057,rs2236058 and rs3766741 were independent risk factors of HUA,and have no significant interaction with essential hypertension,blood urea nitrogen and creatinine.The A-T-A-G-G-C haplotype may associate with HUA.The above results suggest that the polymorphisms of gene Mfn2 may be associated with HUA. |
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