CAJ | 학술논문

目的探讨骨形态发生蛋白-7(bone morphogenetic protein 7,BMP7)基因变异与新疆维吾尔族人糖尿病、胰岛素抵抗的关系.方法采用以流行病学调查为基础的病例-对照研究,选取717名(男276人、女441人)维吾尔族人作为研究对象,根据是否患有糖尿病分成糖尿病组(502例,男191例、女311例)和正常对照组(215人,男85人、女130人).首先在48例维吾尔族糖尿病患者中测序筛查 BMP7基因功能区的变异位点,选取代表性变异位点应用TaqMan-PCR技术在研究人群中进行基因型鉴定并开展病例-对照关联研究.结果在 BMP7基因的功能区共发现5个新的和8个已知的变异位点.BMP7基因的2个代表性变异位点rs6025422、rs17480735均符合Hardy-Weinberg平衡.男性人群中rs6025422变异的AA、AG、GG基因型在糖尿病组及正常对照组中的频率分布差异有统计学意义(P<0.05),但对P值校正后差异无统计学意义(P>0.05),而总人群及女性人群中rs6025422变异基因型频率分布在病例、对照组间差异无统计学意义(P>0.05).男性人群中rs6025422变异不同基因型组间空腹血糖、空腹胰岛素水平、HOMA指数存在差异,并且AA、AG、GG 3组呈现递减趋势(P<0.05),而在总人群及女性人群中未发现上述现象.Logistic分析提示男性人群中rs6025422变异GG基因型是糖尿病的保护性因素(OR=0.637,95%可信区间0.439～0.923,P<0.05).结论 BMP7基因变异位点rs6025422可能与新疆维吾尔族男性糖尿病、胰岛素抵抗相关.
목적 탐토골형태발생단백-7(bone morphogenetic protein 7,BMP7)기인변이여신강유오이족인당뇨병、이도소저항적관계.방법 채용이류행병학조사위기출적병례-대조연구,선취717명(남276인、녀441인)유오이족인작위연구대상,근거시부환유당뇨병분성당뇨병조(502례,남191례、녀311례)화정상대조조(215인,남85인、녀130인).수선재48례유오이족당뇨병환자중측서사사 BMP7기인공능구적변이위점,선취대표성변이위점응용TaqMan-PCR기술재연구인군중진행기인형감정병개전병례-대조관련연구.결과 재 BMP7기인적공능구공발현5개신적화8개이지적변이위점.BMP7기인적2개대표성변이위점rs6025422、rs17480735균부합Hardy-Weinberg평형.남성인군중rs6025422변이적AA、AG、GG기인형재당뇨병조급정상대조조중적빈솔분포차이유통계학의의(P<0.05),단대P치교정후차이무통계학의의(P>0.05),이총인군급녀성인군중rs6025422변이기인형빈솔분포재병례、대조조간차이무통계학의의(P>0.05).남성인군중rs6025422변이불동기인형조간공복혈당、공복이도소수평、HOMA지수존재차이,병차AA、AG、GG 3조정현체감추세(P<0.05),이재총인군급녀성인군중미발현상술현상.Logistic분석제시남성인군중rs6025422변이GG기인형시당뇨병적보호성인소(OR=0.637,95%가신구간0.439～0.923,P<0.05).결론 BMP7기인변이위점rs6025422가능여신강유오이족남성당뇨병、이도소저항상관.
Objective To investigate the association between the genetic variations of the functional region in bone morphogenetic protein gene (BMP7) with type 2 diabetes mellitus in Chinese Uygur individuals. Methods A case-control study was conducted based on epidemiological investigation. A total of 717 Uygur subjects (276 males and 441 females) were selected and divided into two groups: diabetes mellitus group (n=502, 191 males and 311 females) and control group (n=215, 85 males and 130 females). All exons, flanking introns and the promoter regions of BMP7 gene were sequenced in 48 Uygur diabetics. Representative variations were selected according to the minor allele frequency (MAF) and linkage disequilibrium and genotyped using the TaqMan polymerase chain reaction method in 717 Uygur individuals, a relatively isolated general population in a relatively homogeneous environment and a case-control study was conducted to test the association between the genetic variations of BMP7 gene and type 2 diabetes mellitus. Results Five novel and 8 known variations in the BMP7 gene were identified. All genotype distributions were tested for deviations from Hardy-Weinberg equilibrium (P>0.05). There was significant difference of genotype distribution of rs6025422 between type 2 diabetes mellitus and control groups in the male population (P<0.05, P adjusted >0.05), but there was no difference in total and female population (P>0.05). And the means of fasting blood glucose (FBG), fasting insulin and HOMA-index significantly decreased in individuals with AA, AG and GG genotypes of rs6025422 in male population (P<0.05), but not in total and female population (P>0.05). The logistic regression analysis showed that GG genotype of rs6025422 variation might be a protective factor for diabetes in male (OR=0.637,95% confidence interval 0.439-0.923,P<0.05). Conclusion The present study suggests that the rs6025422 polymorphism in BMP7 gene may be associated with diabetes mellitus and insulin resistance in Uygur men.