發(fā)布時間：2018-05-04 03:42

  本文選題：中國 + 人群��； 參考：《安徽大學》2017年碩士論文

【摘要】：背景:血脂異常是由血漿中脂質代謝紊亂引起的一種疾病,是導致動脈粥樣硬化發(fā)生的風險因子之一。血脂異常的發(fā)生,一方面受后天環(huán)境的影響,另一方面受遺傳因素決定。目的:(1)探索在中國原發(fā)性高血壓病人中驗證白細胞分類計數與血脂異常的相關性。(2)探討血漿中總同型半胱氨酸(tHcy)濃度和MTHFRC677T基因型以及二者的交互作用對中國原發(fā)性高血壓患者血漿中脂質濃度變化的影響。(3)研究性別與CYP7A1-278AC和SCARB1 C1050T基因多態(tài)性的交互作用對高脂血癥患者血漿中脂質濃度變化的影響。方法:本研究入組10,866名來自中國腦卒中一級預防研究的高血壓病人。用標準方法檢測血漿中脂質濃度、白細胞數、中性粒細胞數和淋巴細胞數。此外招募了 231名來自安徽省霍邱縣和岳西縣的有著輕中度原發(fā)性高血壓患者。用高效液相色譜法測量血漿中tHcy的濃度,Taqman高通量等位基因分型技術鑒定MTHFR C677T基因型;以及504名患有高脂血癥的病人,用RFLP-PCR方法檢測患者SCARB1 C1050T和CYP7A1-278AC基因型。結果:(1)外周血白細胞分類計數與血漿中TC、LDL和TG濃度都表現出正相關性(所有趨勢分析P0.001),然而與HDL-C濃度呈現負相關性(趨勢分析P0.05)。將血脂二分類(血脂異常/血脂正常)進行亞組分析,我們發(fā)現,與白細胞計數最低組(第一分位)病人相比,白細胞計數最高組(第四分位)的病人患甘油三酯(TG)異常的風險增加1.64倍[95%CI:1.46-1.85];患膽固醇(TC)異常的風險增加1.34倍[95%CI;1.20-1.50];患低密度脂蛋白膽固醇(LDL-C)異常的風險增加1.24倍[95%CI:1.12-1.39]。在淋巴細胞和中性粒細胞中也有相似的發(fā)現。(2)與MTHFR677 CC+CT基因型攜帶者相比,TT基因型攜帶者患高膽固醇血癥(校正后OR[95%CI]:2.7[1.1-5.2];P=0.004)和低密度脂蛋白血癥(OR|95%C1]:2.3[1.1-4.8];P=0.03)的風險更高。TT基因型個體比677 CC+CT基因型個體有著更高濃度的血漿tHcy水平(:0.2[0.003]:P0.001)。當病人血漿tHcy10μmlo/L時患高膽固醇血癥的風險增加(校正后的OR[95%CI]:2.4[1.2-4.7];P=0.01)。此外,當個體為TT基因型且tHcy≥10μmol/L時,病人患有高膽固醇血癥(校正后的OR[95%CI]:4.1[1.8-9.4];P=0.001)和低濃度脂蛋白膽固醇血癥(校正后的OR[95%CJ]:2.4[1.0-6.0];P=0.064)的風險增加。(3)SCARB1 C1050T基因多態(tài)性與性別的交互作用對血漿中LDL-C的濃度有影響(P0.05)。此外,與CYP7A1-278AA基因型攜帶者相比,CYP7A1-278CC基因型患者有著低濃度的血漿總膽固醇和甘油三酯(P0.05)。結論:(1)研究發(fā)現,外周血白細胞分類計數能顯著預測血漿中脂質濃度,并且能夠增加血脂異常的發(fā)生風險。(2)在中國原發(fā)性高血壓病人中,tHcy濃度和MTHFRC677T基因型是導致血脂異常發(fā)生的重要風險因素。(3)此外,我們的結果也表明SCARB1 C1050T和CYP7A1-278AC基因多態(tài)性與性別的交互作用對血脂參數有影響。
[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，

本文編號：1841453