Associations Between Polymorphisms in the Glucocorticoid-Receptor Gene and Cardiovascular Risk Factors in a Chinese Population

被引:19
作者
Yan, Yu-Xiang [1 ,2 ]
Dong, Jing [3 ]
Wu, Li-Juan [1 ,2 ]
Shao, Shuang [1 ,2 ]
Zhang, Jie [1 ,2 ]
Zhang, Ling [1 ,2 ]
Wang, Wei [1 ,2 ]
He, Yan [1 ,2 ]
Liu, You-Qin [3 ]
机构
[1] Capital Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Beijing 100069, Peoples R China
[2] Municipal Key Lab Clin Epidemiol, Beijing, Peoples R China
[3] Capital Med Univ, Beijing Xuanwu Hosp, Phys Examinat Ctr, Beijing, Peoples R China
基金
北京市自然科学基金;
关键词
glucocorticoid receptor gene; polymorphism; cardiovascular disease; risk factor; BODY-MASS INDEX; BLOOD-PRESSURE; IN-VIVO; RESISTANCE/HYPERSENSITIVITY SYNDROMES; ER22/23EK POLYMORPHISM; N363S POLYMORPHISM; DIABETES-MELLITUS; EAST ASIANS; VARIANT; IDENTIFICATION;
D O I
10.2188/jea.JE20130035
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
Background: Glucocorticoid is an important regulator of energy homeostasis. Glucocorticoid receptor (GR) gene polymorphisms that contribute to variability in glucocorticoid sensitivity have been identified. We explored the associations of single-nucleotide polymorphisms (SNPs) of the GR gene with traditional cardiovascular risk factors in the Chinese Han population. Methods: We recruited 762 consecutive adults who underwent a regular physical examination at Beijing Xuanwu Hospital. Blood pressure, glucose, lipid levels (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein [LDL] cholesterol and triglycerides), body mass index (BMI), and waist-to-hip ratio were measured. Fourteen tag SNPs and 5 functional SNPs were selected and genotyped using the high-throughput Sequenom genotyping platform. Differences between genotypes/alleles for each SNP were adjusted for sex and age and tested using a general linear model procedure. Various models of inheritance, including additive, dominant, and recessive, were tested. Results: Among the 19 SNPs examined, 5 markers were associated with cardiovascular risk factors. The rs41423247 GG genotype and the rs7701443 AA genotype were associated with higher BMI and systolic blood pressure (P < 0.0004), and the rs17209251 GG genotype was associated with higher systolic blood pressure (P < 0.0004). Lower systolic blood pressure, total cholesterol, and LDL cholesterol were observed among rs10052957 A allele carriers (P < 0.0004), and lower plasma glucose and LDL-cholesterol concentrations were observed among rs2963156 TT carriers (P < 0.0004). Conclusions: Polymorphism of the GR gene was associated with cardiovascular risk factors and may contribute to susceptibility to cardiovascular disease.
引用
收藏
页码:389 / 395
页数:7
相关论文
共 37 条
[1]   GLUCOCORTICOID RECEPTOR-BETA, A POTENTIAL ENDOGENOUS INHIBITOR OF GLUCOCORTICOID ACTION IN HUMANS [J].
BAMBERGER, CM ;
BAMBERGER, AM ;
DECASTRO, M ;
CHROUSOS, GP .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (06) :2435-2441
[2]   Variations of the human glucocorticoid receptor gene (NR3C1): Pathological and in vitro mutations.and polymorphisms [J].
Bray, PJ ;
Cotton, RGH .
HUMAN MUTATION, 2003, 21 (06) :557-568
[3]   A Novel Point Mutation in the Amino Terminal Domain of the Human Glucocorticoid Receptor (hGR) Gene Enhancing hGR-Mediated Gene Expression [J].
Charmandari, Evangelia ;
Ichijo, Takamasa ;
Jubiz, William ;
Baid, Smita ;
Zachman, Keith ;
Chrousos, George P. ;
Kino, Tomoshige .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2008, 93 (12) :4963-4968
[4]   Glucocorticoid action networks and complex psychiatric and/or somatic disorders [J].
Chrousos, George P. ;
Kino, Tomoshige .
STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS, 2007, 10 (02) :213-219
[5]  
Derijk RH, 2001, J RHEUMATOL, V28, P2383
[6]   A TTHIII1 POLYMORPHISM ON THE 5' FLANKING REGION OF THE GLUCOCORTICOID RECEPTOR GENE (GRL) [J].
DETERAWADLEIGH, SD ;
ENCIO, IJ ;
ROLLINS, DY ;
COFFMAN, D ;
WIESCH, D .
NUCLEIC ACIDS RESEARCH, 1991, 19 (08) :1960-1960
[7]   The relation between two polymorphisms in the glucocorticoid receptor gene and body mass index, blood pressure and cholesterol in obese patients [J].
Di Blasio, AM ;
van Rossum, EFC ;
Maestrini, S ;
Berselli, ME ;
Tagliaferri, M ;
Podestà, F ;
Koper, JW ;
Liuzzi, A ;
Lamberts, SWJ .
CLINICAL ENDOCRINOLOGY, 2003, 59 (01) :68-74
[8]   The N363S polymorphism of the glucocorticoid receptor: Potential contribution to central obesity in men and lack of association with other risk factors for coronary heart disease and diabetes mellitus [J].
Dobson, MG ;
Redfern, CPF ;
Unwin, N ;
Weaver, JU .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (05) :2270-2274
[9]   Distributions of glucocorticoid receptor gene polymorphisms in a Chinese Han population and associations with outcome after major trauma [J].
Duan, Zhao-Xia ;
Gu, Wei ;
Du, Ding-yuan ;
Hu, Ping ;
Jiang, Dong-po ;
Zhu, Pei-Fang ;
Wang, Zheng-Guo ;
Jiang, Jian-Xin .
INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED, 2009, 40 (05) :479-483
[10]   Identification of polymorphisms in the human glucocorticoid receptor gene (NR3C1) in a multi-racial asthma case and control screening panel [J].
Hawkins, GA ;
Amelung, PJ ;
Smith, RS ;
Jongepier, H ;
Howard, TD ;
Koppelman, GH ;
Meyers, DA ;
Bleecker, ER ;
Postma, DS .
DNA SEQUENCE, 2004, 15 (03) :167-173