Genetic variants associated with circulating MMP1 levels near matrix metalloproteinase genes on chromosome 11q21-22 in Taiwanese: interaction with obesity

BMC Medical Genetics

Yu-Lin Ko⁵  Yu-Chen Sun¹  Jeng-Feng Lin⁴  Ming-Sheng Teng⁶  Lung-An Hsu³  Semon Wu²  Hsuan-Li Huang⁴ 

[1] Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan;Department of Life Science, Chinese Culture University, Taipei, Taiwan;Chang Gung University College of Medicine, Taipei, Taiwan;Department of Internal Medicine, Division of Cardiology, Buddhist Tzu Chi General Hospital, Taipei branch, 289 Jianguo Road, Xindian City, Taipei, 231, Taiwan;School of Medicine, Tzu Chi University, Hualien, Taiwan;Department of Medical Research, Buddhist Tzu Chi General Hospital, Taipei branch, Taipei, Taiwan

关键词: Interaction;    Haplotype;    Polymorphism;    Genetic association study;    Matrix metalloproteinase 1;   

Others  :  1177724
DOI  :  10.1186/1471-2350-14-30

 received in 2012-10-04, accepted in 2013-02-11,  发布年份 2013

【 摘 要 】

Background

MMP1 is implicated in the pathogenesis of atherothrombotic cardiovascular disease. We aimed to elucidate genetic determinants of inflammatory marker levels, including circulating MMP1, in Taiwanese, and their association with obesity.

Methods

Five genetic polymorphisms around matrix metalloproteinase genes on chromosome 11q21-22 region were genotyped in 519 subjects.

Results

After adjusting for clinical covariates, two polymorphisms were significantly associated with MMP1 levels, rs1799750 and rs495366, using an additive inheritance model (P = 1.5x10^-4 and P = 2.57x10^-5, respectively). Using dominant model, minor alleles of rs1799750 and rs495366 were associated with higher MMP1 levels (P = 1.3x10^-4 and P = 1.95x10^-5, respectively). In haplotype analysis, two haplotypes inferred from five SNPs (A2GATA and A1GATG) were associated with MMP1 levels (P = 5x10^-4 and P = 8.47x10^-5, respectively). Subgroup and interaction analysis revealed an association of rs1799750 and rs495366 with MMP1 levels only in non-obese subjects (P = 6.66x10^-6 and P = 4.38x10^-5, respectively, and interaction P = 0.008 for rs1799750). Haplotype interaction analysis also showed significant interaction for haplotype A1GATG (interaction P = 0.003).

Conclusions

Genotypes/haplotypes around MMP1 locus are associated with MMP1 levels in Taiwanese. Further, since genotypes/haplotypes near MMP1 locus interact with obesity to set MMP1 levels, genetic determinants for MMP1 level may be different between obese and non-obese individuals.

【 授权许可】

   
2013 Huang et al; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Falk E: Pathogenesis of atherosclerosis. Am Heart J 1999, 138:S421-S425.
• [2]Creemers EE, Cleutjens JP, Smits JF, Daemen MJ: Matrix metalloproteinase inhibition after myocardial infarction: a new approach to prevent heart failure. Circ Res 2001, 89:201-210.
• [3]Dollery CM, Libby P: Atherosclerosis and proteinase activation. Cardiovasc Res 2006, 69:625-635.
• [4]Sluijter JP, de Kleijn DP, Pasterkamp G: Vascular remodeling and protease inhibition–bench to bedside. Cardiovasc Res 2006, 69:595-603.
• [5]Messerli FH: TIMPs, MMPs and cardiovascular disease. Eur Heart J 2004, 25:1475-1476.
• [6]Jones CB, Sane DC, Herrington DM: Matrix metalloproteinases: a review of their structure and role in acute coronary syndrome. Cardiovasc Res 2003, 59:812-823.
• [7]Newby AC: Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol Rev 2005, 85:1-31.
• [8]Galis ZS, Sukhova GK, Lark MW, Libby P: Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 1994, 94:2493-2503.
• [9]Nikkari ST, O’Brien KD, Ferguson M: Interstitial collagenase (MMP-1) expression in human carotid atherosclerosis. Circulation 1995, 92:1393-1398.
• [10]Sukhova GK, Schonbeck U, Rabkin E: Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques. Circulation 1999, 99:2503-2509.
• [11]Morgan AR, Rerkasem K, Gallagher PJ: Differences in matrix metalloproteinase-1 and matrix metalloproteinase-12 transcript levels among carotid atherosclerotic plaques with different histopathological characteristics. Stroke 2004, 35:1310-1315.
• [12]Galt SW, Lindemann S, Allen L: Outside-in signals delivered by matrix metalloproteinase-1 regulate platelet function. Circ Res 2002, 90:1093-1099.
• [13]Nakamura T, Ushiyama C, Suzuki S, Ebihara I, Shimada N, Koide H: Elevation of serum levels of metalloproteinase-1, tissue inhibitor of metalloproteinase-1 and type IV collagen, and plasma levels of metalloproteinase-9 in polycystic kidney disease. Am J Nephrol 2000, 20:32-36.
• [14]Rosas IO, Richards TJ, Konishi K: MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis. PLoS Med 2008, 5:e93.
• [15]Naito Y, Tsujino T, Lee-Kawabata M: Matrix metalloproteinase-1 and -2 levels are differently regulated in acute exacerbation of heart failure in patients with and without left ventricular systolic dysfunction. Hear Vessel 2009, 24:181-186.
• [16]Ghaderian SM, Akbarzadeh Najar R, Tabatabaei Panah AS: Genetic polymorphisms and plasma levels of matrix metalloproteinases and their relationships with developing acute myocardial infarction. Coron Artery Dis 2010, 21:330-335.
• [17]Chen Y, Nixon NB, Dawes PT, Mattey DL: Influence of variations across the MMP-1 and -3 genes on the serum levels of MMP-1 and -3 and disease activity in rheumatoid arthritis. Genes Immun 2012, 13:29-37.
• [18]Rutter JL, Mitchell TI, Butticè G: A single nucleotide polymorphism in the matrix metalloproteinase-1 promoter creates an Ets binding site and augments transcription. Cancer Res 1998, 58:5321-5325.
• [19]Pearce E, Tregouet DA, Samnegård A: Haplotype effect of the matrix metalloproteinase-1 gene on risk of myocardial infarction. Circ Res 2005, 97:1070-1076.
• [20]Affara M, Dunmore BJ, Sanders DA, Johnson N, Print CG, Charnock-Jones DS: MMP1 bimodal expression and differential response to inflammatory mediators is linked to promoter polymorphisms. BMC Genomics 2011, 12:43. BioMed Central Full Text
• [21]Nojiri T, Morita H, Imai Y: Genetic variations of matrix metalloproteinase-1 and -3 promoter regions and their associations with susceptibility to myocardial infarction in Japanese. Int J Cardiol 2003, 92:181-186.
• [22]Ye S, Gale CR, Martyn CN: Variation in the matrix metalloproteinase-1 gene and risk of coronary heart disease. Eur Heart J 2003, 24:1668-1671.
• [23]Flex A, Gaetani E, Angelini F: Pro-inflammatory genetic profiles in subjects with peripheral arterial occlusive disease and critical limb ischemia. J Intern Med 2007, 262:124-130.
• [24]Horne BD, Camp NJ, Carlquist JF: Multiple-polymorphism associations of 7 matrix metalloproteinase and tissue inhibitor metalloproteinase genes with myocardial infarction and angiographic coronary artery disease. Am Heart J 2007, 154:751-758.
• [25]Hlatky MA, Ashley E, Quertermous T: Matrix metalloproteinase circulating levels, genetic polymorphisms, and susceptibility to acute myocardial infarction among patients with coronary artery disease. Am Heart J 2007, 154:1043-1051.
• [26]Han Y, Wu Z, Zhang X: Impact of matrix metalloproteinase-1 gene variations on risk of acute coronary syndrome. Coron Artery Dis 2008, 19:227-230.
• [27]Montes AH, Valle-Garay E, Suarez-Zarracina T: The MMP1 (-16071G/2G) single nucleotide polymorphism associates with the HAART-related lipodystrophic syndrome. AIDS 2010, 24:2499-2506.
• [28]Abd-Allah SH, Shalaby SM, Pasha HF, El-Shal AS, Abou El-Saoud AM: Variation of matrix metalloproteinase 1 and 3 haplotypes and their serum levels in patients with rheumatoid arthritis and osteoarthritis. Genet Test Mol Biomarkers 2012, 16:15-20.
• [29]Cheng YC, Kao WH, Mitchell BD: Genome-wide association scan identifies variants near matrix metalloproteinase (MMP) genes on chromosome 11q21-22 strongly associated with serum MMP-1 levels. Circ Cardiovasc Genet 2009, 2:329-337.
• [30]WHO expert consultation: Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004, 363:157-163.
• [31]Hsu LA, Ko YL, Hsu KH, Ko YH, Lee YS: Genetic variations in the cholesteryl ester transfer protein gene and high density lipoprotein cholesterol levels in Taiwanese Chinese. Hum Genet 2002, 110:57-63.
• [32]Ko YL, Hsu LA, Hsu KH, Ko YH, Lee YS: The interactive effects of hepatic lipase gene promoter polymorphisms with gender and obesity on high-density-lipoprotein cholesterol levels in Taiwanese-Chinese. Atherosclerosis 2004, 172:135-142.
• [33]Wu S, Hsu LA, Teng MS: Association of matrix metalloproteinase 9 genotypes and cardiovascular disease risk factors with serum matrix metalloproteinase 9 concentrations in Taiwanese individuals. Clin Chem Lab Med 2010, 48:543-549.
• [34]Wu TL, Tsao KC, Chang CP, Li CN, Sun CF, Wu JT: Development of ELISA on microplate for serum C-reactive protein and establishment of age-dependent normal reference range. Clin Chim Acta 2002, 322:163-168.
• [35]Chan EC, Chang CP, Wu TL, Wu JT: Enzymatic assay of homocysteine on microtiter plate or a TECAN analyzer using crude lysate containing recombinant methionine-lyase. Ann Clin Lab Sci 2005, 35:155-160.
• [36]Wu TL, Chen Tsai I, Chang PY: stablishment of an in-house ELISA and the reference range for serum amyloid A (SAA) Complementarity between SAA and C-reactive protein as markers of inflammation. Clin Chim Acta 2007, 376:72-76.
• [37]Wu S, Hsu LA, Cheng CF: Effect of obesity on the association between ATF3 gene haplotypes and C-reactive protein level in Taiwanese. Clin Chim Acta 2011, 412:1026-1031.
• [38]Hsu LA, Ko YL, Teng MS: Effect of obesity on the association between common variations in the HNF1A gene region and C-reactive protein level in Taiwanese. Clin Chim Acta 2011, 412:725-729.
• [39]Teng MS, Hsu LA, Wu S, Chang HH, Chou HH, Ko YL: Association between C-reactive protein gene haplotypes and C-reactive protein levels in Taiwanese: interaction with obesity. Atherosclerosis 2009, 204:e64-e69.
• [40]Hsu LA, Chang CJ, Wu S: Association between functional variants of the ICAM1 and CRP genes and metabolic syndrome in Taiwanese subjects. Metabolism 2010, 59:1710-1716.
• [41]Nho YK, Ha E, Yu KI: Matrix metalloproteinase-1 promoter is associated with body mass index in Korean population with aged greater or equal to 50 years. Clin Chim Acta 2008, 396:14-17.
• [42]O'Hara A, Lim FL, Mazzatti DJ, Trayhurn P: Microarray analysis identifies matrix metalloproteinases (MMPs) as key genes whose expression is up-regulated in human adipocytes by macrophage-conditioned medium. Pflugers Arch 2009, 458:1103-1114.
• [43]Li M, Xiao T, Zhang Y: Prognostic significance of matrix metalloproteinase-1 levels in peripheral plasma and tumour tissues of lung cancer patients. Lung Cancer 2010, 69:341-347.
• [44]Liu D, Duan W, Guo H, Xu X, Bai Y: Meta-analysis of associations between polymorphisms in the promoter regions of matrix metalloproteinases and the risk of colorectal cancer. Int J Colorectal Dis 2011, 26:1099-1105.
• [45]Liu D, Guo H, Li Y, Xu X, Yang K, Bai Y: Association between polymorphisms in the promoter regions of matrix metalloproteinases (MMPs) and risk of cancer metastasis: a meta-analysis. PLoS One 2012, 7:e31251.