CAJ | 학술논문

目的研究叉头转录因子3A(FOXO3A)基因rs2802288(G/A)和过氧化物酶体增殖物激活受体辅激活因子1A(PPARGC1A)基因rs8192678 (G/A)与广西汉族长寿及一般人群中2型糖尿病(T2DM)的相关性,并探讨基因间相互作用.方法 2008年7月至2010年8月随机分层选取中国长寿之乡广西永福长寿老人506名(＞ 90岁)和一般人群830名.T2DM诊断依照1999年WHO标准.采用高分辨率熔解曲线(HRM)和聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术检测rs2802288和rs8192678基因型,通过logistic回归进行关联分析,通过风险等位基因累积效应分析及非参数多因子降维法(MDR)评价基因间相互作用.结果隐性遗传模型下,仅在长寿人群中发现FOXO3A基因rs2802288 (G)与T2DM的风险存在正关联(x2=10.933,P＜0.05),并且同PPARGC1A基因rs8192678(A)存在协同作用(x2=9.617,P＜0.05);发生T2DM的风险随风险等位基因数目增加,累积4个风险等位基因的携带者具有最高风险(OR=6.482,P＜0.001).MDR分析提示最佳交互模型为rs2802288、rs8192678和增龄的联合作用模式,最终增加T2DM风险(交叉验证一致性=10/10,P＜0.05).结论 FOXO3A基因rs2802288 (G)是南方汉族长寿人群T2DM的风险等位基因,PPARGC1A基因rs8192678 (A)与其存在协同作用.
목적 연구차두전록인자3A(FOXO3A)기인rs2802288(G/A)화과양화물매체증식물격활수체보격활인자1A(PPARGC1A)기인rs8192678 (G/A)여엄서한족장수급일반인군중2형당뇨병(T2DM)적상관성,병탐토기인간상호작용.방법 2008년7월지2010년8월수궤분층선취중국장수지향엄서영복장수노인506명(＞ 90세)화일반인군830명.T2DM진단의조1999년WHO표준.채용고분변솔용해곡선(HRM)화취합매련식반응-한제성편단장도다태성(PCR-RFLP)기술검측rs2802288화rs8192678기인형,통과logistic회귀진행관련분석,통과풍험등위기인루적효응분석급비삼수다인자강유법(MDR)평개기인간상호작용.결과 은성유전모형하,부재장수인군중발현FOXO3A기인rs2802288 (G)여T2DM적풍험존재정관련(x2=10.933,P＜0.05),병차동PPARGC1A기인rs8192678(A)존재협동작용(x2=9.617,P＜0.05);발생T2DM적풍험수풍험등위기인수목증가,루적4개풍험등위기인적휴대자구유최고풍험(OR=6.482,P＜0.001).MDR분석제시최가교호모형위rs2802288、rs8192678화증령적연합작용모식,최종증가T2DM풍험(교차험증일치성=10/10,P＜0.05).결론 FOXO3A기인rs2802288 (G)시남방한족장수인군T2DM적풍험등위기인,PPARGC1A기인rs8192678 (A)여기존재협동작용.
Objective To explore the correlation of rs2802288 (G/A) in forkhead box class O3A (FOXO3A) gene and rs8192678 (G/A) in peroxisome proliferators-activated receptor-γ coactivator-1 (PPARGC1A) gene to the risk of type 2 diabetes mellitus (T2DM) in longevity and general subjects with Han nationality from Guangxi.Methods By stratified random sampling,a total of 506 longevity subjects (above 90-years old) and 830 general subjects from Guangxi Yongfu County were included in this study from July 2008 to August 2010.The diagnosis for T2DM was based on the 1999 WHO criteria.Based on high resolution melting (HRM) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods,respectively,rs2802288 and rs8192678 were genotyped.The association was estimated by logistic regression.The risk allele accumulation effect and nonparametric multifactor dimension reduction (MDR) were conducted to estimate the gene-gene interaction.Results Based on the recessive genetic model,a positive contribution of FOXO3A rs2802288 (G) for T2DM was detected only in longevity subjects (x2 =10.933,P ＜ 0.05).A synergy between FOXO3A rs2802288 (G) and PPARGC1A rs8192678 (A) (x2 =9.617,P ＜ 0.05) was observed.In addition,the risk of T2DM was increased with the accumulation of risk alleles,and the carriers with 4 risk alleles had the highest risk (OR =6.482,P ＜ 0.001).The MDR analysis indicated the combined effect among rs2802288,rs8192678 and ageing was the best interaction model,resulting in an increased T2DM risk (cross validation consistency =10/10,P ＜ 0.05).Conclusion FOXO3A rs2802288 (G) is associated with T2DM in South Chinese Han longevity subjects,and PPARGC1A rs8192678(A) could increase the risk by a synergy effect.