Associations of the uric acid related genetic variants in SLC2A9 and ABCG2 loci with coronary heart disease risk

BMC Genetics

Meian He²  Tangchun Wu¹  Xiaomin Zhang¹  Jing Feng¹  Gaokun Qiu¹  Binyao Yang¹  Jun Li¹  Xiayun Dai¹  Yaru Li¹  Jing Wang¹  Bing Liu¹  Lixuan Gui¹  Xu Han¹ 

[1] Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, China;MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, 13 Hangkong Rd, Wuhan 430030, Hubei, China

关键词: Gene-environment interaction;    Polymorphism;    Uric acid;    Coronary heart disease;   

Others  :  1121334
DOI  :  10.1186/s12863-015-0162-7

 received in 2014-08-19, accepted in 2015-01-05,  发布年份 2015

【 摘 要 】

Background

Multiple studies investigated the associations between serum uric acid and coronary heart disease (CHD) risk. However, further investigations still remain to be carried out to determine whether there exists a causal relationship between them. We aim to explore the associations between genetic variants in uric acid related loci of SLC2A9 and ABCG2 and CHD risk in a Chinese population.

Results

A case–control study including 1,146 CHD cases and 1,146 controls was conducted. Association analysis between two uric acid related variants (SNP rs11722228 in SLC2A9 and rs4148152 in ABCG2) and CHD risk was performed by logistic regression model. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Compared with subjects with A allele of rs4148152, those with G allele had a decreased CHD risk and the association remained significant in a multivariate model. However, it altered to null when BMI was added into the model. No significant association was observed between rs11722228 and CHD risk. The distribution of CHD risk factors was not significantly different among different genotypes of both SNPs. Among subjects who did not consume alcohol, the G allele of rs4148152 showed a moderate protective effect. However, no significant interactions were observed between SNP by CHD risk factors on CHD risk.

Conclusions

There might be no association between the two uric acid related SNPs with CHD risk. Further studies were warranted to validate these results.

【 授权许可】

   
2015 Han et al.; licensee BioMed Central.

【 参考文献 】

• [1]Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, et al.: Heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation 2013, 127(1):e6-e245.
• [2]Wang F, Xu CQ, He Q, Cai JP, Li XC, Wang D, et al.: Genome-wide association identifies a susceptibility locus for coronary artery disease in the Chinese Han population. Nat Genet 2011, 43(4):345-349.
• [3]Gustavsson J, Mehlig K, Leander K, Strandhagen E, Bjorck L, Thelle DS, et al.: Interaction of apolipoprotein E genotype with smoking and physical inactivity on coronary heart disease risk in men and women. Atherosclerosis 2012, 220(2):486-492.
• [4]Chen JH, Chuang SY, Chen HJ, Yeh WT, Pan WH: Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: a Chinese cohort study. Arthritis Rheum 2009, 61(2):225-232.
• [5]Kathiresan S, Altschuler D, Anand S, Ardissino D, Asselta R, Ball SG, et al.: Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet 2009, 41(3):334-341.
• [6]Fievet C, Nuttens MC, Ducimetiere P, Fruchart JC, Bertrand M, Salomez JL: Relation of arteriographically defined coronary artery disease to serum lipoprotein particles mapped with monoclonal antibodies. Circulation 1991, 84(1):153-159.
• [7]Sundell J, Raitakari OT, Viikari J, Kantola I, Nuutila P, Knuuti J: Both BMI and waist circumference are associated with coronary vasoreactivity in overweight and obese men. Obes Facts 2012, 5(5):693-699.
• [8]Dehghan A, Kottgen A, Yang Q, Hwang S, Kao W, Rivadeneira F, et al.: Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet 2008, 372(9654):1953-1961.
• [9]Avram Z, Krishnan E: Hyperuricaemia–where nephrology meets rheumatology. Rheumatology 2008, 47(7):960-964.
• [10]Tamba S, Nishizawa H, Funahashi T, Okauchi Y, Ogawa T, Noguchi M, et al.: Relationship between the Serum Uric Acid Level, Visceral Fat Accumulation and Serum Adiponectin Concentration in Japanese Men. Intern Med 2008, 47(13):1175-1180.
• [11]Kanellis J, Watanabe S, Li JH, Kang DH, Li P, Nakagawa T, et al.: Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2. Hypertension 2003, 41(6):1287-1293.
• [12]Stark K, Reinhard W, Grassl M, Erdmann J, Schunkert H, Illig T, et al.: Common polymorphisms influencing serum uric acid levels contribute to susceptibility to gout, but not to coronary artery disease. PLoS ONE 2009, 4(11):e7729.
• [13]Smith GD, Ebrahim S: Mendelian randomization: prospects, potentials, and limitations. Int J Epidemiol 2004, 33(1):30-42.
• [14]Kanbay M, Segal M, Afsar B, Kang DH, Rodriguez-Iturbe B, Johnson RJ: The role of uric acid in the pathogenesis of human cardiovascular disease. Heart 2013, 99(11):759-766.
• [15]Kivity S, Kopel E, Maor E, Abu-Bachar F, Segev S, Sidi Y, et al.: Association of serum uric acid and cardiovascular disease in healthy adults. Am J Cardiol 2013, 111(8):1146-1151.
• [16]Ndrepepa G, Braun S, King L, Fusaro M, Tada T, Cassese S, et al.: Uric acid and prognosis in angiography-proven coronary artery disease. Eur J Clin Investig 2013, 43(3):256-266.
• [17]Jeemon P, Prabhakaran D: Does uric acid qualify as an independent risk factor for cardiovascular mortality? Clin Sci 2013, 124(4):255-257.
• [18]Wallace C, Newhouse SJ, Braund P, Zhang F, Tobin M, Falchi M, et al.: Genome-wide association study identifies genes for biomarkers of cardiovascular disease: serum urate and dyslipidemia. Am J Hum Genet 2008, 82(1):139-149.
• [19]Qi L, Parast L, Cai T, Powers C, Gervino EV, Hauser TH, et al.: Genetic susceptibility to coronary heart disease in type 2 diabetes: 3 independent studies. J Am Coll Cardiol 2011, 58(25):2675-2682.
• [20]Chen LK, Lin MH, Lai HY, Hwang SJ, Chiou ST: Uric acid: a surrogate of insulin resistance in older women. Maturitas 2008, 59(1):55-61.
• [21]Moriarity JT, Folsom AR, Iribarren C, Nieto FJ, Rosamond WD: Serum uric acid and risk of coronary heart disease: Atherosclerosis Risk in Communities (ARIC) study. Ann Epidemiol 2000, 10(3):136-143.
• [22]Stark K, Reinhard W, Neureuther K, Wiedmann S, Sedlacek K, Baessler A, et al.: Association of common polymorphisms in GLUT9 gene with gout but not with coronary artery disease in a large case–control study. PLoS ONE 2008, 3(4):e1948.
• [23]Qin L, Yang Z, Gu HX, Lu S, Shi Q, Xing Y, et al. Association between serum uric acid levels and cardiovascular disease in middle-aged and elderly Chinese individuals. Bmc Cardiovasc Disor. 2014;14.
• [24]Chien KL, Hsu HC, Sung FC, Su TC, Chen MF, Lee YT: Hyperuricemia as a risk factor on cardiovascular events in Taiwan: the Chin-Shan Community Cardiovascular Cohort study. Atherosclerosis 2005, 183(1):147-155.
• [25]Yang Q, Kottgen A, Dehghan A, Smith AV, Glazer NL, Chen MH, et al.: Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors. Circ Cardiovasc Genet 2010, 3(6):523-530.
• [26]Caulfield MJ, Munroe PB, O’Neill D, Witkowska K, Charchar FJ, Doblado M, et al.: SLC2A9 is a high-capacity urate transporter in humans. PLoS Med 2008, 5(10):e197.
• [27]Kolz M, Johnson T, Sanna S, Teumer A, Vitart V, Perola M, et al.: Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet 2009, 5(6):e1000504.
• [28]Guan M, Zhou D, Ma W, Chen Y, Zhang J, Zou H: Association of an intronic SNP of SLC2A9 gene with serum uric acid levels in the Chinese male Han population by high-resolution melting method. Clin Rheumatol 2011, 30(1):29-35.
• [29]Reitsma PH, Reinhard W, Stark K, Neureuther K, Wiedmann S, Sedlacek K, et al.: Association of common polymorphisms in GLUT9 gene with gout but not with coronary artery disease in a large case–control study. PLoS ONE 2008, 3(4):e1948.
• [30]Karns R, Zhang G, Sun G, Rao Indugula S, Cheng H, Havas-Augustin D, et al.: Genome-wide association of serum uric acid concentration: replication of sequence variants in an island population of the Adriatic coast of Croatia. Ann Hum Genet 2012, 76(2):121-127.
• [31]Gunjača G, Boban M, Pehlić M, Zemunik T, Budimir D, Kolčić I, et al.: Predictive value of 8 genetic loci for serum uric acid concentration. Croat Med J 2010, 51(1):23-31.
• [32]Yang B, Mo Z, Wu C, Yang H, Yang X, He Y, et al.: A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population. BMC Med Genet 2014, 7:10.
• [33]Palmer TM, Nordestgaard BG, Benn M, Tybjaerg-Hansen A, Davey Smith G, Lawlor DA, Timpson NJ: Association of plasma uric acid with ischaemic heart disease and blood pressure: mendelian randomisation analysis of two large cohorts. BMJ 2013, 347:f4262.
• [34]Luke MM, Kane JP, Liu DM, Rowland CM, Shiffman D, Cassano J, et al.: A polymorphism in the protease-like domain of apolipoprotein(a) is associated with severe coronary artery disease. Arterioscler Thromb Vasc Biol 2007, 27(9):2030-2036.
• [35]Hamajima N, Okada R, Kawai S, Hishida A, Morita E, Yin G, et al.: Significant association of serum uric acid levels with SLC2A9 rs11722228 among a Japanese population. Mol Genet Metab 2011, 103(4):378-382.
• [36]Sun X, Jiang F, Zhang R, Tang SS, Chen M, Peng DF, et al.: Serum uric acid levels are associated with polymorphisms in the SLC2A9, SF1, and GCKR genes in a Chinese population. Acta Pharmacol Sin 2014, 35(11):1421-1427.
• [37]Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, Arveiler D, Rajakangas AM, Pajak A: Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents. Circulation 1994, 90(1):583-612.
• [38]Puavilai G, Chanprasertyotin S, Sriphrapradaeng A: Diagnostic criteria for diabetes mellitus and other categories of glucose intolerance: 1997 criteria by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (ADA), 1998 WHO consultation criteria, and 1985 WHO criteria. World Health Organization. Diabetes Res Clin Pract 1999, 44(1):21-26.
• [39]Zhou L, Zhang X, He M, Cheng L, Chen Y, Hu FB, et al.: Associations between single nucleotide polymorphisms on chromosome 9p21 and risk of coronary heart disease in Chinese Han population. Arterioscler Thromb Vasc Biol 2008, 28(11):2085-2089.
• [40]Kim JY, Oh S, Chang MR, Cho YG, Park KH, Paek YJ, et al.: Comparability and utility of body composition measurement vs. anthropometric measurement for assessing obesity related health risks in Korean men. Int J Clin Pract 2013, 67(1):73-80.
• [41]Li S, Zhao JH, Luan J, Langenberg C, Luben RN, Khaw KT, et al.: Genetic predisposition to obesity leads to increased risk of type 2 diabetes. Diabetologia 2011, 54(4):776-782.
• [42]Didelez V, Sheehan N: Mendelian randomization as an instrumental variable approach to causal inference. Stat Methods Med Res 2007, 16(4):309-330.
• [43]van der Harst P, Bakker SJ, de Boer RA, Wolffenbuttel BH, Johnson T, Caulfield MJ, et al.: Replication of the five novel loci for uric acid concentrations and potential mediating mechanisms. Hum Mol Genet 2010, 19(2):387-395.
• [44]Chen P, Zhao L, Zou P, Xu H, Lu A, Zhao P: The contribution of the ABCG2 C421A polymorphism to cancer susceptibility: a meta-analysis of the current literature. BMC Cancer 2012, 12:383. BioMed Central Full Text