新疆哈萨克族人群高血压与血浆免疫球蛋白GN-糖基组的关联分析

Association between Hypertension and IgG N-glycome in Xinjiang Kazakh Population

目的分析新疆哈萨克族人群高血压与血浆免疫球蛋白G(Ig G)N-糖基组的关联,寻找高血压疾病状态的潜在分子标志物。方法采用简单随机抽样,选取2014年2—6月于新疆伊犁哈萨克自治州琼博拉乡卫生院建立健康档案的哈萨克族居民92例为研究对象,根据高血压诊断标准,将研究对象分为血压正常组(n=35)、正常高值组(n=27)和高血压组(n=30)。采用液相色谱-电喷雾质谱联用技术检测血浆Ig G N-糖基组。结果每例受试者的各Ig G亚型均检测到G0、G0F、G0FN、G0N、G1、G1F、G1FN、G1FNS、G1FS、G1N、G1NS、G1S、G2、G2F、G2FN、G2FNS、G2FS、G2N、G2NS、G2S等20种聚糖结构。除G0外,不同Ig G亚型各N-聚糖水平比较,差异均有统计学意义(P<0.05)。高血压组Ig G1亚型G0F、G0FN、G1FS水平高于血压正常组,G2、G2FS水平低于血压正常组;正常高值组Ig G1亚型G2F水平低于血压正常组,高血压组Ig G1亚型G2F水平低于血压正常组、正常高值组(P<0.05)。正常高值组Ig G2/3亚型G0FN、G0N水平高于血压正常组,G2、G2S水平低于血压正常组;高血压组Ig G2/3亚型G0、G0F、G0FN、G0N水平高于血压正常组,G2、G2F、G2FS、G2NS、G2S水平低于血压正常组,G2FN、G2FNS水平低于血压正常组、正常高值组(P<0.05)。高血压组Ig G4亚型G0FN水平高于血压正常组、正常高值组(P<0.05)。正常高值组Ig G1亚型半乳糖基化水平低于血压正常组,高血压组Ig G1亚型半乳糖基化水平低于血压正常组和正常高值组(P<0.05)。正常高值组、高血压组Ig G2/3亚型半乳糖基化、唾液酸化水平低于血压正常组,高血压组Ig G2/3亚型半乳糖基化水平低于正常高值组(P<0.05)。结论新疆哈萨克族人群不同血压状态与其血浆Ig G N-糖基组谱型变化相关,Ig G1亚型G2F水平及Ig G1、Ig G2/3亚型半乳糖基化水平的改变可能是该人群高血压疾病状态潜在的早期预警分子标志物和治疗新靶点。

Objective To analyze the association between hypertension and IgG N-glycome in Xinjiang Kazakh population, and to explore the potential biomarkers of the state of hypertension disease. Methods Ninety - two Kazakh participants who had established health records in health center of Qapqal County, Xinjiang Yili Kazakh Autonomous Prefecture from February to June 2014 were recruited as research objects by simple random sampling method. According to the diagnostic criteria of hypertension, the subjects were divided into normal blood pressure group （ n = 35 ）, normal high - value group （ n = 27） and hypertension group （n = 30 ）. The plasma IgG N-glycome was detected by liquid chromatography - electrospray ionization mass spectrometry. Results Twenty glycans （GO, GOF, GOFN, GON, G1, G1F, G1FN, G1FNS, G1FS, GIN, GINS, G1S, G2, G2F, G2FN, G2FNS, G2FS, G2N, G2NS, G2S） were all detected in various IgG subtypes of each subject. Except for GO, there were significant differences in each N-glycome levels of different IgG subtypes （ P 〈 0. 05 ）. The level of GOF, GOFN and G1FS of IgG1 subtypes in hypertension group was higher than that in normal blood pressure group, while the levels of G2 and G2FS was lower; the level of G2F of IgG1 subtypes in normal high - value group was lower than that in normal blood pressure group, the level of G2F of IgG1 subtypes in hypertension group was lower than that in normal blood pressure group and normal high - value group （ P 〈 0. 05 ）. In normal high - value group, the level of GOFN and GON of IgG2/3 subtypes was higher than that in normal blood pressure group, and the level of G2 and G2S was lower; in hypertension group, the level of GO, GOF, GOFN and GON of IgG2/3 subtypes was higher and the level of G2, G2F, G2FS, G2NS and G2S was lower than that in normal blood pressure group, anal the level of G2FN and G2FNS was lower than that in normal blood pressure group and normal high - value group （ P 〈 0. 05）. The levels of GOFN of IgG4 subtypes in hypertension group was higher than that in normal blood pressure group and normal high - value group （ P 〈 0. 05 ）. The level of galacosylation of IgG1 subtypes in normal high - value group was significantly lower than that in normal blood pressure group, and the level of galaeosylation of IgG1 subtypes in hypertension group was significantly lower than that in normal blood pressure group and normal high - value group （ P 〈 0. 05）. The levels of galacosylation and sialylation of IgG2/3 subtypes in normal high - value group and hypertension group were significantly lower than those in normal blood pressure group, and the level of galacosylation of IgG2/3 subtypes in hypertension group was significantly lower than that in normal high - va!ue group （P 〈 0.05 ）. Conclusion The different states of blood pressure is associated with its plasma IgG N-glycome changes of： Xinjiang Kazakh population, the changes in the levels of G2F of IgG1 subtypes and galactosylated levels of IgG1 and IgG2/3 subtypes may be the potential biomarkers and novel therapeutic targets for hypertension status among this population.