本文選題：中國(guó) + 人群　； 參考：《安徽大學(xué)》2017年碩士論文

【摘要】：背景:血脂異常是由血漿中脂質(zhì)代謝紊亂引起的一種疾病,是導(dǎo)致動(dòng)脈粥樣硬化發(fā)生的風(fēng)險(xiǎn)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(guó)原發(fā)性高血壓病人中驗(yàn)證白細(xì)胞分類計(jì)數(shù)與血脂異常的相關(guān)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(duì)中國(guó)原發(fā)性高血壓患者血漿中脂質(zhì)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(duì)高脂血癥患者血漿中脂質(zhì)濃度變化的影響。方法:本研究入組10,866名來(lái)自中國(guó)腦卒中一級(jí)預(yù)防研究的高血壓病人。用標(biāo)準(zhǔn)方法檢測(cè)血漿中脂質(zhì)濃度、白細(xì)胞數(shù)、中性粒細(xì)胞數(shù)和淋巴細(xì)胞數(shù)。此外招募了 231名來(lái)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(cè)量血漿中tHcy的濃度,Taqman高通量等位基因分型技術(shù)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(cè)患者SCARB1 C1050T和CYP7A1-278AC基因型。結(jié)果:(1)外周血白細(xì)胞分類計(jì)數(shù)與血漿中TC、LDL和TG濃度都表現(xiàn)出正相關(guān)性(所有趨勢(shì)分析P0.001),然而與HDL-C濃度呈現(xiàn)負(fù)相關(guān)性(趨勢(shì)分析P0.05)。將血脂二分類(血脂異常/血脂正常)進(jìn)行亞組分析,我們發(fā)現(xiàn),與白細(xì)胞計(jì)數(shù)最低組(第一分位)病人相比,白細(xì)胞計(jì)數(shù)最高組(第四分位)的病人患甘油三酯(TG)異常的風(fēng)險(xiǎn)增加1.64倍[95%CI:1.46-1.85];患膽固醇(TC)異常的風(fēng)險(xiǎn)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(fēng)險(xiǎn)增加1.24倍[95%CI:1.12-1.39]。在淋巴細(xì)胞和中性粒細(xì)胞中也有相似的發(fā)現(xiàn)。(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(fēng)險(xiǎn)更高。TT基因型個(gè)體比677 CC+CT基因型個(gè)體有著更高濃度的血漿tHcy水平(:0.2[0.003]:P0.001)。當(dāng)病人血漿tHcy10μmlo/L時(shí)患高膽固醇血癥的風(fēng)險(xiǎn)增加(校正后的OR[95%CI]:2.4[1.2-4.7];P=0.01)。此外,當(dāng)個(gè)體為TT基因型且tHcy≥10μmol/L時(shí),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(fēng)險(xiǎn)增加。(3)SCARB1 C1050T基因多態(tài)性與性別的交互作用對(duì)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(jié)論:(1)研究發(fā)現(xiàn),外周血白細(xì)胞分類計(jì)數(shù)能顯著預(yù)測(cè)血漿中脂質(zhì)濃度,并且能夠增加血脂異常的發(fā)生風(fēng)險(xiǎn)。(2)在中國(guó)原發(fā)性高血壓病人中,tHcy濃度和MTHFRC677T基因型是導(dǎo)致血脂異常發(fā)生的重要風(fēng)險(xiǎn)因素。(3)此外,我們的結(jié)果也表明SCARB1 C1050T和CYP7A1-278AC基因多態(tài)性與性別的交互作用對(duì)血脂參數(shù)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，

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