糖基化终末产物受体基因单核苷酸多态性与动脉僵硬度及波反射的关系

Arterial stiffness and wave reflection in relation to genetic polymorphisms in receptor of advanced glycation end products

目的:探究糖基化终末产物(AGEs)受体基因(RAGE)Gly82Ser(rs2070600)、-374T/A(rs1800624)多态性与动脉僵硬度及波反射的关系。方法:研究对象为上海郊区的社区居民。采用美国应用生物系统公司(ABI)SnapShot方法进行基因分型。采用酶联免疫吸附测定(ELISA)方法测定血浆AGEs浓度,并经对数转换后进行统计分析。使用SphygmoCor系统测量颈股脉搏波传导速度(cfPWV)和中心及外周反射波增强指数(cAI、pAI),分别评估动脉僵硬度和波反射。结果:968名研究对象年龄(55.2±13.0)岁,其中女性607名(62.7%),高血压患者361例(37.3%),糖尿病及糖尿病前期患者85例(8.8%)。Gly82Ser(GlyGly 56.3%、GlySer 38.6%、SerSer 5.1%)与-374T/A(TT 65.4%、TA31.4%、AA 3.2%)基因型频率均符合Hardy-Weinberg平衡(均P>0.05)。Gly82Ser与-374T/A各基因型之间血浆AGEs浓度无显著差异(均P>0.05);但在调整相关危险因素后,-374A等位基因携带者AGEs浓度显著高于TT纯合子(5.5 mg/L比4.9 mg/L,P=0.02)。随着Gly82Ser变异Ser等位基因个数的增加,pAI呈上升趋势(β=0.14,P=0.049),但基因型之间cfPWV无明显差异(均P>0.05);-374T/A各基因型之间cfPWV与中心及pAI均无显著差异(均P>0.05)。结论:RAGE基因可能与血浆AGEs浓度及动脉波反射仅存在较弱相关。

Objective To investigate the arterial stiffness and wave reflection in relation to the Gly82Ser （rs2070600） and -374T/A （rs1800624） polymorphisms in receptor of advanced glycation end products （RAGE） in a Chinese population. Methods The study participants were recruited from a residential area in the suburb of Shanghai. Genotyping was performed using the SnapShot method. Plasma advanced glycation end products （AGEs） concentration was measured by the en- zyme linked immunosorbent assay （ELISA） and logarithmically transformed for statistical analysis. Carotid-femoral pulse wave velocity （PWV） and peripheral and central augmentation indexes were determined using the Sphygmo Cor system as measures of arterial stiffness and wave reflection, respectively. Results The 968 subjects had a mean age of （55.2±13.0） years, and included 607 （62.7%） women, 361 （37.3%） hypertensive patients, and 85 （8.8%） diabetic or prediabetic patients. The genotype frequencies of G]y82Ser（GlyGly 56.3%, GlySer 38.6%, and SerSer 5.1%） and -374T/A （Tr 65.4%, TA 31.4%, and AA 3.2%） polymorphisms were in accordance with the Hardy-Weinberg equilibrium（all P〉0.05）. Plasma AGEs concentration did not differ across the Gly82Ser or -374T/A genotypes（all P〉0.05）. However, after adjustment for confounders, the difference in plasma AGEs concentration between -374A allele carriers and -374Tr homozygotes reached statistical signifi- cance （5.5 mg/L vs. 4.9 mg/L, P=0.02）. None of the genetic associations with carotid-femoral PWV or central and peripheral augmentation indexes reached statistical significance （all P〉0.05）, except for a borderline significant association between peripheral augmentation index and the Gly82Ser polymorphism （β=0.14, P=-0.049）. Conclusions The genetic polymorphisms in RAGE were weakly associated with plasma AGEs concentration and peripheral augmentation index.