阻塞性睡眠呼吸暂停对2型糖尿病患病影响的遗传修饰作用

Genetic modification effects of obstructive sleep apnea on the morbidity of type 2 diabetes mellitus

目的采用多基因遗传风险评分探讨阻塞性睡眠呼吸暂停(obstructive sleep apnea,OSA)对2型糖尿病患病影响的遗传修饰作用,为对2型糖尿病进行精准化的预防和控制提供理论依据。方法研究对象选自2011—2012年建立的基于北京市房山社区的心脑血管慢性病队列,最终共纳入5144名研究对象,收集其一般人口学资料、行为生活方式、既往病史、体检检查等信息,使用Berlin量表采集其OSA临床特征信息,对2型糖尿病相关的26个单核苷酸多态性位点进行基因型检测,并采用加权遗传风险评分计算研究对象的遗传风险。使用SAS 9.4软件采用多因素logistic回归模型分析OSA风险、糖尿病遗传风险评分与2型糖尿病患病的关联和联合作用。结果(1)在调整了年龄、性别、受教育程度、婚姻状态、体质指数、体育锻炼、饮酒和吸烟等因素后,OSA高风险人群相较于OSA低风险人群具有更高的糖尿病患病风险(OR=1.381,95%CI:1.193~1.599,P<0.01);高糖尿病遗传风险人群比低糖尿病遗传风险人群有着更高的糖尿病患病风险(OR=1.587,95%CI:1.309~1.925,P<0.01)。(2)在中、高糖尿病遗传风险的人群中OSA高风险能够显著增加糖尿病的患病风险(中风险人群:调整后OSA高风险的OR值为1.439,95%CI为1.170~1.769,P<0.01;高风险人群:调整后OSA高风险的OR值为1.422,95%CI为1.073~1.885,P<0.05)。低糖尿病遗传风险人群中,OSA风险高低对糖尿病患病的影响差异无统计学意义(P>0.05)。(3)进一步分析两因素联合作用,高遗传风险与OSA高风险之间存在联合作用,能够显著增加糖尿病的患病风险(调整后OR=2.331,95%CI:1.758~3.090,P<0.01)。结论OSA高风险对2型糖尿病患病的影响存在遗传个体差异,OSA高风险和高遗传风险评分具有联合作用,能够显著提高2型糖尿病的患病风险。

Objective To explore the genetic modification effects of obstructive sleep apnea(OSA)on the morbidity of type 2 diabetes mellitus(T2 DM)by polygenic genetic risk score,and to provide the basis for precise prevention and control of T2 DM.Methods The subjects were the baseline data of the Fangshan/family-based ischemic stroke cohort from 2011 to 2012,the included subjects were 5144 cases;the information of general demographics,lifestyle factors,history of chronic diseases and physical examination was collected.The Berlin scale was used to collect the clinic features of OSA.The 26 single nucleotide polymorphism sites(SNPs)related to T2 DM were detected by genotyping.The genetic risk of all subjects was assessed by weighted genetic risk score method.The multiple logistic regression model was used to analyze the correlation and joint effects of OSA risk and genetic risk score to T2 DM morbidity.The used software was SAS 9.4 Results After adjusting age,sex,marriage status,education level,body mass index(BMI),physical exercise,drinking,smoking,the diabetes risk in residents with high OSA risk was significantly higher than that in residents with low OSA risk(OR=1.381,95%CI:1.193-1.599,P<0.01);the diabetes risk in residents with high diabetes genetic risk was significantly higher than that in residents with low diabetes genetic risk(OR=1.587,95%CI:1.309-1.925,P<0.01).The high OSA risk in residents with middle or high diabetes genetic risk could increase the diabetes risk(middle risk residents:after adjusting,OR=1.439,95%CI:1.170-1.769,P<0.01;high risk residents:after adjusting,OR=1.422,95%CI:1.073-1.885,P<0.05,respectively);the OSA risk in residents with low diabetes genetic risk did not influence the diabetes morbidity(P>0.05).After analyzing the joint effects,there was the joint effects between high diabetes genetic risk and high OSA risk,which could increase the diabetes risk(after adjusting,OR=2.331,95%CI:1.758-3.090,P<0.01).Conclusion High OSA risk affects T2 DM patients with genetic individual differences,there are the significant joint effects between high diabetes genetic risk and high OSA risk,which can increase significantly the T2 DM risk.