Haplotypes and 5A/6A polymorphism of the matrix metalloproteinase-3 gene in coronary disease: Case–control study and a meta-analysis

• Published in: Atherosclerosis Vol. 208; no. 1; pp. 171 - 176
• Main Authors: Koch, Werner, de Waha, Antoinette, Hoppmann, Petra, Schömig, Albert, Kastrati, Adnan
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01-01-2010; Elsevier
• Subjects: Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular; Case-Control Studies; Coronary Disease - genetics; Coronary heart disease; Female; Haplotype; Haplotypes - genetics; Heart; Humans; Male; Matrix metalloproteinase; Matrix Metalloproteinase 3 - genetics; Medical sciences; Meta-analysis; Middle Aged; MMP3; Myocardial infarction; Myocardial Infarction - genetics; Polymorphism, Single Nucleotide; Myocardial infarction; Matrix metalloproteinase; Haplotype; MMP3; Meta-analysis; Vascular disease; Atherosclerosis; Cardiovascular disease; Case control study; Myocardial disease; Coronary heart disease; Polymorphism
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2009.08.021

Abstract Objective Matrix metalloproteinase-3 and its gene, MMP3 , have been implicated in atherosclerotic diseases of coronary arteries. We conducted a haplotype analysis to examine the role of common variation of MMP3 in myocardial infarction (MI) and a meta-analysis to combine available evidence on the association between the 5A/6A polymorphism (rs3025058) and coronary diseases. Methods and results Genotype distributions of haplotype-tagging single nucleotide polymorphisms (rs522616, rs650108, rs569444, rs635746) and rs3025058 were not significantly different between a group with MI ( n = 3657) and a control group ( n = 1211) ( p ≥ 0.24). Five major haplotypes were established, and their frequencies were not substantially different between the case and control groups ( p ≥ 0.11). In a meta-analysis of 15 studies (10,061 cases, 8048 controls), the overall risk of coronary disease was not different between the carriers of the 5A allele and 6A6A genotype of rs3025058 (OR, 1.00; 95% CI, 0.85–1.19). Moderate trends of a reduced risk in the 5A allele carriers of European ancestry (OR, 0.87; 95% CI, 0.76–1.00) and an increased risk in the 5A allele carriers from East Asia (OR, 1.33; 95% CI, 0.94–1.90) were observed. Conclusions Individual polymorphisms and haplotypes of MMP3 were not associated with MI in a German case–control study. Evidence was obtained to suggest different risk effects of rs3025058 between Europeans and East Asians.