Association Study Of The Hyperplasia Suppressor Gene Single Nucleotide Polymorphisms And Essential Hypertension In The Central Han Chinese Population

BackgroundThe gene HSG(Hyperplasiasuppressor gene,also named Mitofusion-2,Mfn2)was initially isolated using differential display technology and its expression was reduced in vascular smooth muscle cells(VSMCs)of the spontaneously hypertensive rat(SHR),which suggested that the HSG/Mfn2 gene might be a hypertension-related gene.Subsequent research demonstrated that HSG/Mfn2 gene overexpression can suppress the proliferation of VSMCs,which suggested that Mfn2 was an important proliferation inhibitor factor.We inferred that HSG/Mfn2 gene might be one of hypertension candidate genes and the polymorphisms of HSG/Mfn2 gene were associated with risk for essential hypertension.Objective To explore the association between the three polymorphisms(rs873457,rs2236384,rs2295281,rs4846085,rsl474868 and rs17037564)of the gene encoding the mitofusion-2 and essential hypertension by performing a case-control study in the Central Han Chinese population.MethodsWe recruited 300 hypertensive patients and 300 control subjects of Central Han Chinese population from Octber 2015 to July 2017.Genotyping was performed to identify rs873457,rs2236384,rs2295281,rs4846085,rs1474868 and rs17037564 polymorphisms using the TaqMan assay.Comparisons of allelic and genotypic frequencies between cases and controls were made by using the chi-square test.Logistic regression analyses were performed to investigate the relationships between the six polymorphisms of HSG/Mfn2 gene under different genetic models(additive,dominant and recessive models).Linkage disequilibrium and haplotype analysis was conducted using the SHEsis software.Results1.The SNPs(rs873457,rs17037564)genotype frequency of HSG/Mfn2 gene were significantly different between EH group and NT group((P<0.05),)The percentage of the rs873457 C allele and the rs17037564 A allele carriers were significantly higher in the patients with hypertension than in the controls(P<0.05).No significant difference in the genotype and allele frequency distribution of SNP rs2236384,rs2295281,rs4846085 and rs 1474868 was observed between the EH group and the NT group.2.Logistic regression analysis indicated that CC+CG genotype of rs873457 and AA+AG genotype of rs17037564 were significantly associated with increased risk of EH(OR=1.788,95%CI[1.640-1.970],P=0.025,OR=0.766,95%CI[0.594-0.987],P=0.039 respectively)after adjustment for the potential covariates.No significant association between rs2236384,rs4846085,rsl474868,rs2295281 polymorphisms and EH risk was observed.3.When stratified by gender,Logistic regression analysis indicated that CC+CG genotype of rs873457 and AA+AG genotype of rs17037564 were significantly associated with increased risk of EH(OR=1.792,95%CI[1.594-2.056],P=0.032,OR=0.704,95%CI[0.501-0.989],P=0.043 respectively)after adjustment for the potential covariates in the subgroup of males,but not in the subgroup of females.As for rs2236384,rs2295281,rs4846085 or rs1474868 polymorphisms,no significant association was found in either subgroup(P>0.05).4.Linkage disequilibrium was detected between the rs873457,rs2236384,rs2295281,rs4846085,rs1474868 and rs17037564 polymorphisms.Five haplotypes were detected in the SHEsis haplotype analyses.Haplotype analysis indicated that the G-T-T-C-C-A haplotype was positively correlated(OR=1.59,95%CI[0.6980-3.743],P=0.048)with EH;there was might a negative correlation between C-G-T-T-C-A haplotype and EH(OR=0.635,95%CI[0.203-1.992],P=0.433).The other haplotypes were not associated with hypertension risk.ConclusionsThe present study demonstrated that the rs873457 and rs17037564 polymorphisms of the HSG/Mfn2 gene were associated with EH risk in the Central Han Chinese population especially in male subjects.The C allele of rs873457 and the A allele of rs17037564 was observed to be a risk factor for EH,while the T allele of rs4846085 was found to be a potentially protective factor.No significant association were observed between rs2236384,rs4846085,rs1474868,rs2295281 polymorphism and EH..The rs873457,rs2236384,rs2295281,rs4846085,rs1474868 and rs17037564 polymorphisms of the HSG/Mfn2 gene were in close linkage disequilibrium.Haplotype analyses observed that the C-G-T-T-C-A haplotype migtht be a protective haplotype for EH,while the G-T-T-C-C-A haplotype increased the risk of EH.