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瘦素基因G2548A多態(tài)性及環(huán)境因素與膽囊膽固醇結(jié)石關(guān)聯(lián)性研究

發(fā)布時間:2018-06-04 05:41

  本文選題:單核苷酸多態(tài)性 + 膽囊膽固醇結(jié)石。 參考:《四川大學(xué)學(xué)報(醫(yī)學(xué)版)》2017年03期


【摘要】:目的評估瘦素基因(LEP)G2548A單核苷酸多態(tài)性(SNP)及環(huán)境因素與膽囊膽固醇結(jié)石發(fā)病危險的關(guān)聯(lián)性,同時探究該多態(tài)性位點(diǎn)與環(huán)境因素對膽囊膽固醇結(jié)石的發(fā)生是否存在交互作用。方法收集符合條件的膽囊膽固醇結(jié)石患者200例進(jìn)行1∶2匹配的病例對照研究(對照組400例)。應(yīng)用高分辨率熔解曲線(highresolution melting,HRM)技術(shù)作基因分型檢測并對結(jié)果進(jìn)行測序驗(yàn)證,采用多因素分析探索基因多態(tài)性及血清瘦素水平與膽囊膽固醇結(jié)石的關(guān)聯(lián)性。采用多因子降維法(multifactor dimensionality reduction,MDR)探索基因與環(huán)境因素的交互作用對膽囊膽固醇結(jié)石發(fā)病的影響。結(jié)果通過HRM基因分型檢測,共得到LEP G2548A位點(diǎn)3種基因型,分別為野生型GG(52例),突變雜合型GA(192例)和突變純合型AA(356例)。該SNP位點(diǎn)在對照組中的基因型分布均符合Hardy-Weinberg遺傳平衡(P0.05)。LEP G2548A位點(diǎn)AA基因型攜帶者血清瘦素水平高于GA/GG基因型攜帶者,差異有統(tǒng)計學(xué)意義(H=6.83,P0.05)。多因素條件logistic回歸分析結(jié)果顯示,在調(diào)整年齡、性別以及其他影響因素后,膽固醇結(jié)石危險因素是:血清高瘦素水平[標(biāo)準(zhǔn)偏回歸系數(shù)(β)=0.781,比值比(OR)=5.012,95%可信區(qū)間(95%CI):3.248~7.734]、LEP G2548A突變純合子AA基因型(β=0.527,OR=2.292,95%CI:1.012~5.193)、膽結(jié)石家族史(β=0.267,OR=2.984,95%CI:1.329~6.700)、高收縮壓(β=0.239,OR=1.927,95%CI:1.140~3.255)以及吸煙(β=0.236,OR=1.717,95%CI:1.006~2.928);而保護(hù)因素是:飲濃茶習(xí)慣(β=-0.477,OR=0.552,95%CI:0.336~0.907)與堅(jiān)持鍛煉(β=-0.252,OR=0.591,95%CI:0.395~0.882)。MDR分析結(jié)果顯示,飲茶習(xí)慣-LEP G2548A多態(tài)性-血清瘦素水平組合為最優(yōu)基因-環(huán)境交互作用模型。結(jié)論 LEP G2548A位點(diǎn)AA基因型可能通過影響血清瘦素水平增加發(fā)生膽囊膽固醇結(jié)石風(fēng)險,而攜帶AA基因型且有飲淡茶習(xí)慣的血清高瘦素水平者對膽囊膽固醇結(jié)石可能更加易感。
[Abstract]:Objective to evaluate the association between the single nucleotide polymorphisms (SNPs) and environmental factors of leptin gene Lepco G2548A and the risk of cholecystolithiasis, and to explore the interaction between the polymorphism and environmental factors on the occurrence of cholecystolithiasis. Methods 200 patients with cholecystolithiasis were collected and matched at 1:2 (control group, 400 cases). The high resolution melting curve (HRM) technique was used to detect the genotyping and the results were sequenced. Multivariate analysis was used to explore the relationship between gene polymorphism and serum leptin level and gallbladder cholesterol stone. Multifactor dimensionality reduction was used to explore the effect of gene interaction with environmental factors on the development of cholesterol gallstone. Results three genotypes of LEP G2548A were obtained by HRM genotyping. They were wild type GG(52, mutant heterozygous GA(192 and homozygous AA(356. The genotype distribution of the SNP locus in the control group was in accordance with the Hardy-Weinberg genetic balance. The serum leptin levels of the AA genotype carriers were higher than those of the GA/GG genotype carriers, and the difference was statistically significant. The results of multivariate conditional logistic regression analysis showed that after adjusting for age, sex and other influencing factors, 鑳嗗浐閱囩粨鐭沖嵄闄╁洜绱犳槸:琛,

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