中国人群高脂血症遗传风险和环境因素调查

发布时间：2018-05-04 03:42

  本文选题：中国 + 人群　； 参考：《安徽大学》2017年硕士论文

【摘要】：背景:血脂异常是由血浆中脂质代谢紊乱引起的一种疾病,是导致动脉粥样硬化发生的风险因子之一。血脂异常的发生,一方面受后天环境的影响,另一方面受遗传因素决定。目的:(1)探索在中国原发性高血压病人中验证白细胞分类计数与血脂异常的相关性。(2)探讨血浆中总同型半胱氨酸(tHcy)浓度和MTHFRC677T基因型以及二者的交互作用对中国原发性高血压患者血浆中脂质浓度变化的影响。(3)研究性别与CYP7A1-278AC和SCARB1 C1050T基因多态性的交互作用对高脂血症患者血浆中脂质浓度变化的影响。方法:本研究入组10,866名来自中国脑卒中一级预防研究的高血压病人。用标准方法检测血浆中脂质浓度、白细胞数、中性粒细胞数和淋巴细胞数。此外招募了 231名来自安徽省霍邱县和岳西县的有着轻中度原发性高血压患者。用高效液相色谱法测量血浆中tHcy的浓度,Taqman高通量等位基因分型技术鉴定MTHFR C677T基因型;以及504名患有高脂血症的病人,用RFLP-PCR方法检测患者SCARB1 C1050T和CYP7A1-278AC基因型。结果:(1)外周血白细胞分类计数与血浆中TC、LDL和TG浓度都表现出正相关性(所有趋势分析P0.001),然而与HDL-C浓度呈现负相关性(趋势分析P0.05)。将血脂二分类(血脂异常/血脂正常)进行亚组分析,我们发现,与白细胞计数最低组(第一分位)病人相比,白细胞计数最高组(第四分位)的病人患甘油三酯(TG)异常的风险增加1.64倍[95%CI:1.46-1.85];患胆固醇(TC)异常的风险增加1.34倍[95%CI;1.20-1.50];患低密度脂蛋白胆固醇(LDL-C)异常的风险增加1.24倍[95%CI:1.12-1.39]。在淋巴细胞和中性粒细胞中也有相似的发现。(2)与MTHFR677 CC+CT基因型携带者相比,TT基因型携带者患高胆固醇血症(校正后OR[95%CI]:2.7[1.1-5.2];P=0.004)和低密度脂蛋白血症(OR|95%C1]:2.3[1.1-4.8];P=0.03)的风险更高。TT基因型个体比677 CC+CT基因型个体有着更高浓度的血浆tHcy水平(:0.2[0.003]:P0.001)。当病人血浆tHcy10μmlo/L时患高胆固醇血症的风险增加(校正后的OR[95%CI]:2.4[1.2-4.7];P=0.01)。此外,当个体为TT基因型且tHcy≥10μmol/L时,病人患有高胆固醇血症(校正后的OR[95%CI]:4.1[1.8-9.4];P=0.001)和低浓度脂蛋白胆固醇血症(校正后的OR[95%CJ]:2.4[1.0-6.0];P=0.064)的风险增加。(3)SCARB1 C1050T基因多态性与性别的交互作用对血浆中LDL-C的浓度有影响(P0.05)。此外,与CYP7A1-278AA基因型携带者相比,CYP7A1-278CC基因型患者有着低浓度的血浆总胆固醇和甘油三酯(P0.05)。结论:(1)研究发现,外周血白细胞分类计数能显著预测血浆中脂质浓度,并且能够增加血脂异常的发生风险。(2)在中国原发性高血压病人中,tHcy浓度和MTHFRC677T基因型是导致血脂异常发生的重要风险因素。(3)此外,我们的结果也表明SCARB1 C1050T和CYP7A1-278AC基因多态性与性别的交互作用对血脂参数有影响。
[Abstract]:Background: dyslipidemia is a disease caused by disorder of lipid metabolism in plasma and is one of the risk factors leading to atherosclerosis. The occurrence of dyslipidemia is affected by the acquired environment on the one hand, and by genetic factors on the other. Objective: to explore the correlation between leukocyte classification and dyslipidemia in Chinese patients with essential hypertension. The effect of sex and CYP7A1-278AC and SCARB1 C1050T gene polymorphism on plasma lipid concentration in patients with hyperlipidemia was studied. Methods: the study included 10866 hypertensive patients from the first-class study of stroke prevention in China. Plasma lipid concentration, leukocyte count, neutrophil count and lymphocyte count were measured by standard method. In addition, 231 patients with mild to moderate essential hypertension were recruited from Huoqiu County and Yuexi County, Anhui Province. MTHFR C677T genotypes were identified by high throughput allelic typing of tHcy in plasma by high performance liquid chromatography (HPLC), and SCARB1 C1050T and CYP7A1-278AC genotypes were detected by RFLP-PCR in 504 patients with hyperlipidemia. Results (1) there was a positive correlation between leukocyte count in peripheral blood and plasma levels of TCG-LDL and TG (all trend analysis showed a positive correlation (P0.001), but a negative correlation with HDL-C concentration (trend analysis P0.05). Subgroup analysis of blood lipids (dyslipidemia / normolipidemia), we found that compared with patients with the lowest white blood cell count (first point), In the highest leukocyte count group (quartile), the risk of abnormal triglyceride was increased by 1.64 times [95%CI:1.46-1.85], the risk of abnormal cholesterol was increased by 1.34 times [95CIN 1.20-1.50], the risk of low density lipoprotein cholesterol (LDL-C) was increased by 1.24 times [95%CI:1.12-1.39]. A similar finding was found in lymphocytes and neutrophils.) the risk of hypercholesterolemia (adjusted OR [95%CI]: 2.7 [1.1-5.2] P0. 004 and OR 95] 2.3 [1.1-4.8] P0.03] was higher in TTT genotype carriers than in MTHFR677 CC CT genotype carriers (adjusted OR [95%CI] 2.7 [1.1-5.2] P0. 004). Compared with 677CC CT genotype individuals, the plasma tHcy level was higher than that of 677CC CT genotypes. The plasma tHcy level was 0. 2 [0.003]: P0. 001. The risk of hypercholesterolemia was increased with plasma tHcy10 渭 mlo/L (adjusted OR [95%CI]: 2.4 [1.2-4.7]). In addition, when individuals were TT genotype and tHcy 鈮，

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