论文部分内容阅读
Vascular proliferative disorders,such as atherosclerosis and restenosis,are the most common causes of severe cardiovascular diseases.In previous studies,we identified a novel hyperplasia suppressor gene (HSG,later renamed mitochondrial GTPase mitofusin 2/MFN2),whose expression was markedly reduced in hyperproliferative vascular smooth muscle cells (VSMCs).In another study,we found seven single nucleotide polymorphisms (SNPs) of HSG/MFN2 significantly associated with essential hypertension (EH).Mutations in HSG/MFN2 are also the most common causes of axonal CharcotMarieTooth disease (CMT2).Over 60 mutations have been reported,mainly causing autosomal dominant disease.However,whether and how MFN2 plays a pleiotropic effect in CMT2 and EH has not been studied as far as we know.In the present study,we sequenced through the 40k region of HSG/MFN2 gene and its flanks via dual strand Sanger sequencing for 100 EH patients and 50 normal subjects.Association analyses were performed and the most significant result was one synonymous mutation (NM_014874.3:c.150C > A,p.lle50Ile) in exon 3 with P =0.040.Nine mutations in exons were detected,among which one synonymous mutation (NM_014874.3:c.408A > T,p.Val136Val) in exon 5 was previously reported to associate with CMT2 in a Chinese population.Interestingly,these two mutations in exon 3 and exon 5 were in strong linkage disequilibrium (LD).Moreover,two mutations in intron 2 and intron 4 seemed to suppress the potential harm of the two mutations in exon 3 and exon 5,respectively.The present study indicated an interesting pleiotropic role of HSG/MFN2 on EH and CMT2.