新疆不同地区肾虚血瘀型耳聋患者COCH基因突变位点及与肾虚血瘀型的关系探讨

TRelationship between kidney deficiency and blood stasis type deafness and COCH gene mutation in different regions of Xinjiang

目的分析新疆不同地区耳聋患者COCH基因突变位点、频率,并探讨其与肾虚血瘀型的关系。方法确定新疆两个地区195例耳聋患者纳入病例组,包括:阿勒泰地区99例、哈密市96例;配对设计207例健康人为对照组,包括:阿勒泰地区104例、哈密市103例。所有受检者均收集外周血提取DNA,采用聚合酶链反应(PCR)产物直接测序方法进行COCH第4、5、12外显子基因突变检测,中医辨证分型为肾虚血瘀型患者和非肾虚血瘀型患者。结果在COCH第12外显子上,测得3种基因突变形式:1760A>T、1791A>G、2461T>C;进一步比较发现,对照组三种基因突变形式中,哈密市维吾尔族与阿勒泰地区哈萨克族人群中2461T>C基因突变位点的差异具有统计学意义(P<0.05)。肾虚血瘀型患者占所有耳聋患者的58.5%。发生COCH基因突变均与不同地区及中医辨证分型存在线性相关(P<0.05)。结论耳聋患者中肾虚血瘀型占比较高。新发现突变位点丰富了新疆COCH基因突变和多态性图谱,为进一步研究新疆耳聋遗传筛查和基因库的建立奠定基础。肾虚血瘀可能是COCH基因突变差异的原因之一,具有一定的民族和地域特征。建议结合防治新思路,以补肾活血法对耳聋进行治疗。

Objective To analyze the location and frequency of COCH gene mutations in deaf patients in different regions of Xinjiang,and to explore its relationship with kidney deficiency and blood stasis.Methods The survey included 195 patients with deafness in Xinjiang,including 99 in Altay region and 96 in Hami City;207 normal controls,including 104 in Altay region and 103 in Hami City.All subjects collected peripheral blood extracted DNA and detected the mutations of exon 4,5 and 12 of COCH by direct sequencing of polymerase chain reaction(PCR)products.TCM syndrome differentiation is patients with kidney deficiency and blood stasis type and patients with non-kidney deficiency and blood stasis type.Results IOn exon 12 of COCH,three mutant forms of the gene were measured:1760A>T,1791A>G,and 2461T>C;further comparison revealed that among the three mutant forms of the gene in the control group,the difference between the 2461T>C mutant loci in the Uyghur population in Hami and the Kazakh population in the Altay region was statistically significant(P<0.05).Patients with the kidney deficiency and blood stasis type accounted for 58.5%of all deaf patients.The occurrence of COCH gene mutations were all linearly correlated with different regions and with TCM identification typing(P<0.05).Conclusion Kidney deficiency and blood stasis type account for a high proportion of deaf patients.The newly discovered mutations and polymorphisms enriched the COCH gene mutation and polymorphism map in Xinjiang,laying a foundation for further research on the genetic screening and gene pool establishment of Xinjiang deafness.Kidney deficiency and blood stasis may be one of the reasons for the difference in COCH gene mutations,with certain ethnic and regional characteristics.It is recommended to combine the new idea of prevention and treatment of deafness with the method of tonifying the kidney and activating the blood.