Tribbles同源蛋白1 rs2954029单核苷酸多态性与非酒精性脂肪性肝病及冠状动脉粥样硬化性心脏病的相关性分析

刘群; 栾桂萍; 高慧; 赵本田; 杜水仙; 刘守胜; 辛永宁

doi:10.3969/j.issn.1001-5256.2019.06.030

Tribbles同源蛋白1 rs2954029单核苷酸多态性与非酒精性脂肪性肝病及冠状动脉粥样硬化性心脏病的相关性分析

DOI: 10.3969/j.issn.1001-5256.2019.06.030

1. 青岛大学医学院
2. 青岛市市立医院感染科
3. 青岛市市立医院消化内二科
4. 青岛市市立医院中心实验室
5. 青岛市消化疾病重点实验室

基金项目:

国家自然科学基金面上项目(31770837)；

详细信息

中图分类号: R575.5;R541.4
计量
- 文章访问数: 589
- HTML全文浏览量: 41
- PDF下载量: 78
- 被引次数: 0
出版历程
- 收稿日期: 2019-01-11
- 出版日期: 2019-06-20

Association of TRIB1 rs2954029 single nucleotide polymorphism with the risk of nonalcoholic fatty liver disease and coronary heart disease

Medical College of Qingdao University

Research funding:

摘要

摘要:
目的在青岛地区汉族人群中,探讨Tribbles同源蛋白1（TRIB1） rs2954029单核苷酸多态性与非酒精性脂肪性肝病（NAFLD）及冠状动脉粥样硬化性心脏病（CHD）的相关性,并探讨该基因多态性对血脂水平的影响。方法随机选取2017年1月-2017年11月收入青岛市市立医院的146例NAFLD患者为NAFLD组,155例CHD患者为CHD组,156例NAFLD合并CHD患者为合并组,175例健康对照人群为对照组。采集空腹静脉血进行生化检测和TRIB1 rs2954029基因型测定。应用χ2检验分析样本是否符合Hardy-Weinberg平衡;计数资料组间比较采用χ2检验;计量资料组间比较采用t检验或Wilcoxon秩和检验;比值比（OR）及其95%可信区间（95%CI）应用非条件logistic回归模型计算。结果 CHD组与对照组相比,合并组与NAFLD组相比,rs2954029位点基因型频率及等位基因频率分布差异均无统计学意义（P值均> 0. 05）。CHD组与对照组中,rs2954029 AT+AA携带者与TT携带者相比,发病风险未增加（OR=1. 496,95%CI...
- 非酒精性脂肪性肝病 /
- 冠心病 /
- 多态性,单核苷酸
Abstract:
Objective To investigate the association of TRIB1 rs2954029 single nucleotide polymorphism with nonalcoholic fatty liver disease (NAFLD) and coronary heart disease (CHD) and its influence on blood lipids in the Chinese Han population in Qingdao, China.Methods A total of 146 patients with NAFLD, 155 patients with CHD, and 156 patients with NAFLD and CHD, who were admitted to Qingdao Municipal Hospital from January to November, 2017, were enrolled as NAFLD group, CHD group, and NAFLD + CHD group, respectively, and 175 healthy individuals were enrolled as control group. Fasting venous blood samples were collected for biochemical analysis and TRIB1 rs2954029 genotyping. The chi-square test was used to analyze whether the distribution of genotypes was in accordance with the Hardy-Weinberg equilibrium. The chi-square test was used for comparison of categorical data between groups; the t-test and the Wilcoxon rank-sum test were used for comparison of continuous data between groups. The unconditioned logistic regression model was used to calculate odds ratio (OR) and its 95% confidence interval (CI) . Results There were no significant differences in rs2954029 genotype/allele frequency and distribution between the CHD group and the control group, as well as between the NAFLD + CHD group and the NAFLD group (all P > 0. 05) . In the CHD group and the control group, rs2954029 AT + AA carriers did not have an increased risk of CHD compared with rs2954029 TT carriers (OR = 1. 496, 95% CI: 0. 947-2. 363, P = 0. 084) ; in the NAFLD + CHD group and the NAFLD group, rs2954029 AT + AA carriers did not have an increased risk of CHD compared with rs2954029 TT carriers (OR = 1. 361, 95% CI: 0. 832-2. 227, P =0. 219) ; there were still no significant differences after adjustment for sex, age, and body mass index. In the whole population and the NAFLD group, there were no significant differences in biochemical parameters between the individuals carrying A allele and those not carrying this allele (P > 0. 05) ; in the CHD group and the NAFLD + CHD group, the individuals carrying A allele had a significantly higher level of triglyceride than those not carrying this allele (Z =-1. 986, -2. 521, all P < 0. 05) ; in the control group, the individuals carrying A allele had a significantly higher level of total cholesterol than those not carrying this allele (Z =-2. 653, P < 0. 05) . Conclusion In the Chinese Han population in Qingdao, TRIB1 rs2954029 single nucleotide polymorphism does not increase the risk of CHD in NAFLD patients.
- non-alcoholic fatty liver disease /
- coronary disease /
- polymorphism, single nucleotide

HTML全文

参考文献(30)

[1]KOCH LK, YEH MM.Nonalcoholic fatty liver disease (NAFLD) :Diagnosis, pitfalls, and staging[J].Ann Diagn Pathol, 2018, 37 (1) :83-90.

[2]WONG VW.Current prevention and treatment options for NAFLD[J].Adv Exp Med Biol, 2018, 1061 (1) :149-157.

[3]DAY CP, JAMES OF.Steatohepatitis:A tale of two"hits"?[J].Gastroenterology, 1998, 114 (4) :842-845.

[4]TILG H, MOSCHEN AR.Evolution of inflammation in nonalcoholic fatty liver disease:The multiple parallel hits hypothesis[J].Hepatology, 2010, 52 (5) :1836-1846.

[5]LUCAS C, LUCAS G, LUCAS N, et al.A systematic review of the present and future of non-alcoholic fatty liver disease[J].Clin Exp Hepatol, 2018, 4 (3) :165-174.

[6]FRIEDMAN SL, NEUSCHWANDER-TETRI BA, RINELLA M, et al.Mechanisms of NAFLD development and therapeutic strategies[J].Nat Med, 2018, 24 (7) :908-922.

[7]LI XL, SUI JQ, LU LL, et al.Gene polymorphisms associated with non-alcoholic fatty liver disease and coronary artery disease:A concise review[J].Lipids Health Dis, 2016, 15 (1) :53.

[8]HSU SH, JANG MH, TORNG PL, et al.Positive association between small dense low-density lipoprotein cholesterol concentration and biomarkers of inflammation, thrombosis, and prediabetes in non-diabetic adults[J].J Atheroscler Thromb, 2018, 275 (1) :87-95.

[9]ZHOU H, LIU JC, LUO GH, et al.Application of coronary artery disease-reporting and data system in risk factor analysis of patients with coronary artery disease[J].J Jilin Univ:Med Edit, 2017, 43 (3) :617-621. (in Chinese) 周宏, 刘进才, 罗光华, 等.冠状动脉疾病报告与数据系统在冠心病患者危险因素分析中的应用[J].吉林大学学报:医学版, 2017, 43 (3) :617-621.

[10]KATSIKI N, AL-RASADI K, MIKHAILIDIS DP.Lipoprotein (a) and cardiovascular risk:The show must go on[J].Curr Med Chem, 2017, 24 (10) :989-1006.

[11]MANTOVANI A, BALLESTRI S, LONARDO A, et al.Cardiovascular disease and myocardial abnormalities in nonalcoholic fatty liver disease[J].Dig Dis Sci, 2016, 61 (5) :1246-1267.

[12]ESLAM M, VALENTI L, ROMEO S.Genetics and epigenetics of NAFLD and NASH:Clinical impact[J].J Hepatol, 2018, 68 (2) :268-279.

[13]SOOKOIAN S, PIROLA CJ.Genetic predisposition in nonalcoholic fatty liver disease[J].Clin Mol Hepatol, 2017, 23 (1) :1-12.

[14]BURKHARDT R, TOH SA, LAGOR WR, et al.Trib1 is a lipidand myocardial infarction-associated gene that regulates hepatic lipogenesis and VLDL production in mice[J].J Clin Invest, 2010, 120 (12) :4410-4414.

[15]MAKISHIMA S, BOONVISUT S, ISHIZUKA Y, et al.Sin3A-associated protein, 18 kDa, a novel binding partner of TRIB1, regulates MTTP expression[J].J Lipid Res, 2015, 56 (6) :1145-1152.

[16]IWAMOTO S, BOONVISUT S, MAKISHIMA S, et al.The role of TRIB1 in lipid metabolism;from genetics to pathways[J].Biochem Soc Trans, 2015, 43 (5) :1063-1068.

[17]OLLILA HM, UTGE S, KRONHOLM E, et al.TRIB1 constitutes a molecular link between regulation of sleep and lipid metabolism in humans[J].Transl Psychiatry, 2012, 2 (1) :97.

[18]AUNG LH, YIN RX, WU DF, et al.Association of the TRIB1tribbles homolog 1 gene rs17321515 A>G polymorphism and serum lipid levels in the Mulao and Han populations[J].Lipids Health Dis, 2011, 10 (1) :230.

[19]DOUVRIS A, SOUBEYRAND S, NAING T, et al.Functional analysis of the TRIB1 associated locus linked to plasma triglycerides and coronary artery disease[J].J Am Heart Assoc, 2014, 3 (3) :884.

[20]WANG L, JING J, FU Q, et al.Association study of genetic variants at newly identified lipid gene TRIB1 with coronary heart disease in Chinese Han population[J].Lipids Health Dis, 2015, 14 (1) :46.

[21]KITAMOTO A, KITAMOTO T, NAKAMURA T, et al.Association of polymorphisms in GCKR and TRIB1 with nonalcoholic fatty liver disease and metabolic syndrome traits[J].Endocr J, 2014, 61 (7) :683-689.

[22]SPELIOTES EK, YERGES-ARMSTRONG LM, WU J, et al.Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits[J].PLo S Genet, 2011, 7 (3) :1324.

[23]National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association;Fatty Liver Expert Committee, Chinese Medical Doctor Association.Guidelines of prevention and treatment for nonalcoholic fatty liver disease:A 2018 update[J].J Clin Hepatol, 2018, 34 (5) :947-957. (in Chinese) 中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会.非酒精性脂肪性肝病防治指南 (2018年更新版) [J].临床肝胆病杂志, 2018, 34 (5) :947-957.

[24]BALLESTRI S, LONARDO A, BONAPACE S, et al.Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease[J].World J Gastroenterol, 2014, 20 (7) :1724-1745.

[25]MO XQ, HUANG C, SONG QQ, et al.Correlation study of cystatin C and insulin resistance in type 2 diabetes mellitus patients with non-alcoholic fatty liver[J].China Med Herald, 2017, 14 (24) :78-80. (in Chinese) 莫小庆, 黄春, 宋青青, 等.2型糖尿病伴非酒精性脂肪肝患者胱抑素C与胰岛素抵抗的相关性研究[J].中国医药导报, 2017, 14 (24) :78-80.

[26]PARK MH, KIM N, LEE JY, et al.Genetic loci associated with lipid concentrations and cardiovascular risk factors in the Korean population[J].J Med Genet, 2011, 48 (1) :10-15.

[27]VARBO A, BENN M, TYBJAERG-HANSEN A, et al.TRIB1and GCKR polymorphisms, lipid levels, and risk of ischemic heart disease in the general population[J].Arterioscler Thromb Vasc Biol, 2011, 31 (2) :451-457.

[28]SUMEGI K, JAROMI L, MAGYARI L, et al.Functional variants of lipid level modifier MLXIPL, GCKR, GALNT2, CILP2, AN-GPTL3 and TRIB1 genes in healthy Roma and Hungarian populations[J].Pathol Oncol Res, 2015, 21 (3) :743-749.

[29]JAROMI L, CSONGEI V, POLGAR N, et al.Triglyceride level-influencing functional variants of the ANGPTL3, CILP2, and TRIB1 loci in ischemic stroke[J].Neuromolecular Med, 2011, 13 (3) :179-186.

[30]GARCIA-RIOS A, PEREZ-MARTINEZ P, MATA P, et al.Polymorphism at the TRIB1 gene modulates plasma lipid levels:Insight from the Spanish familial hypercholesterolemia cohort study[J].Nutr Metab Cardiovasc Dis, 2011, 21 (12) :957-963.

施引文献

资源附件(0)

访问统计