Progress in the associations between polymorphisms in peroxisome proliferator-activated receptor gamma and coronary heart disease
-
摘要: 核受体过氧化物酶体增殖物激活受体γ(PPARγ)通过调控相关基因表达而增强胰岛素敏感性,促进脂肪细胞分化和脂肪形成,具有抗动脉粥样硬化、抗炎、抗氧化等特性。人类PPARγ基因(PPARG)含有数以千计的变异位点,其中位于外显子区的rs1801282和rs3856806,启动子区的rs10865710和rs7649970四个位点被广泛报道与冠心病(CHD)显著相关。在关联机制上,PPARG基因变异主要通过引起血脂紊乱、升高血压、增加体脂含量、促进胰岛素抵抗等机制而增加CHD的风险。本文就PPARG基因多态性与CHD的相关性及关联机制作一综述。
-
关键词:
- 过氧化物酶体增殖物激活受体γ /
- PPARG /
- 多态性 /
- 冠心病 /
- 血脂
Abstract: By regulating the expression of related genes,nuclear receptor peroxisome proliferator-activated receptor gamma(PPARγ) enhances insulin sensitivity,promotes adipocyte differentiation, and promotes adipogenesis. PPARγ has the characteristics of anti-atherosclerosis,anti-inflammation, and anti-oxidation. Human PPARγ gene(PPARG) contains thousands of polymorphic loci,among them two polymorphisms(rs1801282 and rs3856806) in the exon regions and two polymorphisms(rs10865710 and rs7649970) in the promoter regions were widely reported to be significantly associated with coronary heart disease(CHD). In mechanisms,the polymorphisms in PPARG increase the risk of CHD mainly by causing dyslipidemia,elevating blood pressure,increasing body fat content, and promoting insulin resistance. This review concentrates on the relationships between the polymorphisms in PPARG and CHD,as well as the underlying mechanisms. -
-
[1] Zhang X,Lv S,Guo C,et al.Gene-gene interaction between PPARG and CYP1A1 gene on coronary artery disease in the Chinese Han Population[J].Oncotarget,2017,8(21):34398-34404.
[2] Ding X,Wang R,Liu L,et al.Interaction between peroxisome proliferator-activated receptor gamma and smoking on cardiovascular disease[J].Physiol Behav,2016,153:28-32.
[3] Dallongeville J,Iribarren C,Ferrières J,et al.Peroxisome proliferator-activated receptor gamma polymorphisms and coronary heart disease[J].PPAR Res,2009,2009:543746.
[4] Nikitin AG,Chistiakov DA,Minushkina LO,et al.Association of the CYBA,PPARGC1A,PPARG3,and PPARD gene variants with coronary artery disease and metabolic risk factors of coronary atherosclerosis in a Russian population[J].Heart Vessels,2010,25(3):229-236.
[5] Li L,Cheng LX,Nsenga R,et al.Association between Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma 2 and myocardial infarction in the Chinese Han population[J].Clin Cardiol,2006,29(7):300-304.
[6] Wang LP,Zhao LR,Cui HW,et al.Association between PPARγ2 Pro12Ala polymorphism and myocardial infarction and obesity in Han Chinese in Hohhot,China[J].Genet Mol Res,2012,11(3):2929-2938.
[7] Maciejewska-Skrendo A,Pawlik A,Sawczuk M,et al.PPARA,PPARD and PPARG gene polymorphisms in patients with unstable angina[J].Gene,2019,711:143947.
[8] Hasan NS,Kamel SA,Hamed M,et al.Peroxisome proliferator-activated receptor-γ polymorphism (rs1801282) is associated with obesity in Egyptian patients with coronary artery disease and type 2 diabetes mellitus[J].J Genet Eng Biotechnol,2017,15(2):409-414.
[9] Vogel U,Segel S,Dethlefsen C,et al.PPARgamma Pro12Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes[J].BMC Med Genet,2009,10:52.
[10] Schneider JG,Schiekofer S,von Eynatten M,et al.The proline 12 alanine substitution in the PPARgamma2 gene is associated with increased extent of coronary artery disease in men[J].Exp Clin Endocrinol Diabetes,2009,117(9):519-521.
[11] Ho JS,Germer S,Tam CH,So WY,et al.Association of the PPARG Pro12Ala polymorphism with type 2 diabetes and incident coronary heart disease in a Hong Kong Chinese population[J].Diabetes Res Clin Pract,2012,97(3):483-491.
[12] Ridker PM,Cook NR,Cheng S,et al.Alanine for proline substitution in the peroxisome proliferator-activated receptor gamma-2 (PPARG2) gene and the risk of incident myocardial infarction[J].Arterioscler Thromb Vasc Biol,2003,23(5):859-863.
[13] Galgani A,Valdes A,Erlich HA,et al.Homozygosity for the Ala allele of the PPARγ2 Pro12Ala polymorphism is associated with reduced risk of coronary artery disease[J].Dis Markers,2010,29(5):259-264.
[14] 范例,吴士尧,严毓勤.过氧化体增殖剂激活受体γ基因Pro12Ala多态性与冠心病的关系[J].中国综合临床,2010,26(10),1043-1046.
[15] 王玉霞,宋玉萍,周静,等.PPARγ2基因Pro12Ala多态性与2型糖尿病合并冠心病的相关性[J].第四军医大学学报.2009,30(24):3107-3109.
[16] Tobin MD,Braund PS,Burton PR,et al.Genotypes and haplotypes predisposing to myocardial infarction:a multilocus case-control study[J].Eur Heart J,2004,25(6):459-467.
[17] Blüher M,Klemm T,Gerike T,et al.Lack of association between peroxisome proliferator-activated receptor-gamma-2 gene variants and the occurrence of coronary heart disease in patients with diabetes mellitus[J].Eur J Endocrinol,2002,146(4):545-551.
[18] Rhee EJ,Kwon CH,Lee WY,et al.No association of Pro12Ala polymorphism of PPAR-gamma gene with coronary artery disease in Korean subjects[J].Circ J,2007,71(3):338-342.
[19] Yilmaz-Aydogan H,Kurnaz O,Kurt O,et al.Effects of the PPARG P12A and C161T gene variants on serum lipids in coronary heart disease patients with and without Type 2 diabetes[J].Mol Cell Biochem,2011,358(1-2):355-363.
[20] Wu Z,Lou Y,Jin W,et al.The Pro12Ala polymorphism in the peroxisome proliferator-activated receptor gamma-2 gene (PPARγ2) is associated with increased risk of coronary artery disease:a meta-analysis[J].PLoS One,2012,7(12):e53105.
[21] Qian Y,Li P,Zhang J,et al.Association between peroxisome proliferator-activated receptor-alpha,delta,and gamma polymorphisms and risk of coronary heart disease:A case-control study and meta-analysis[J].Medicine (Baltimore),2016,95(32):e4299.
[22] Zhou X,Chen J,Xu W.Association between C1431T polymorphism in peroxisome proliferator-activated receptor-γ gene and coronary artery disease in Chinese Han population[J].Mol Biol Rep,2012,39(2):1863-1868.
[23] Wang XL,Oosterhof J,Duarte N.Peroxisome proliferator-activated receptor gamma C161-->T polymorphism and coronary artery disease[J].Cardiovasc Res.1999,44(3):588-594.
[24] Chao TH,Li YH,Chen JH,et al.The 161TT genotype in the exon 6 of the peroxisome-proliferator-activated receptor gamma gene is associated with premature acute myocardial infarction and increased lipid peroxidation in habitual heavy smokers[J].Clin Sci (Lond),2004,107(5):461-466.
[25] Oladi M,Nohtani M,Avan A,et al.Impact of the C1431T polymorphism of the peroxisome proliferator activated receptor-gamma (PPAR-γ) gene on fasted serum lipid levels in patients with coronary artery disease[J].Ann Nutr Metab,2015,66(2-3):149-154.
[26] 郑萍,邢晓春,秦勤.PPARγC161-T基因多态性对冠心病发病的影响[J].继续医学教育,2018,32(7):83-85.
[27] Ding S,Liu L,Zhuge QC,et al.The meta-analysis of the association of PPARG P12A,C161T polymorphism and coronary heart disease[J].Wien Klin Wochenschr,2012,124(19-20):671-677.
[28] Wang P,Wang Q,Yin Y,et al.Association between Peroxisome proliferator-activated receptor gamma gene polymorphisms and atherosclerotic diseases:A meta-analysis of case-control studies[J].J Atheroscler Thromb,2015,22(9):912-925.
[29] 蒋健刚,兰景良,杜晓马.过氧化物酶体增殖物激活受体-γ2基因多态性与冠病易感性及血脂水平的关系研究[J].浙江医学,2016,38(7):485-488.
[30] Brunstrom M,Carlberg B.Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels:A systematic review and meta-analysis[J].JAMA Intern Med,2018,178(1):28-36.
[31] Cai G,Zhang X,Weng W,et al.Associations between PPARG polymorphisms and the risk of essential hypertension[J].PLoS One,2017,12(7):e0181644.
[32] 李丹丹,杨旭明.过氧化物酶体增殖物激活受体γ2基因Pro12Ala多态性与原发性高血压关系的meta分析[J].临床心血管病杂志,2018,34(9):880-886.
[33] 张晓伏,李新茹,薛新宏,等.过氧化物酶体增殖物激活受体γ2基因Pro12Ala多态性与宁夏回、汉族原发性高血压的关系[J].临床心血管病杂志,2018,34(1):47-51.
-
计量
- 文章访问数: 171
- PDF下载数: 26
- 施引文献: 0
下载: