Assessment of genetic risk for myocardial infarction

Yoshiji Yamada; Hitoshi Matsuo; Tomonori Segawa; Sachiro Watanabe; Kimihiko Kato; Takeshi Hibino; Kiyoshi Yokoi; Sahoko Ichihara; Norifumi Metoki; Hidemi Yoshida; Kei Satoh; Yoshinori Nozawa

doi:10.1160/TH06-02-0117

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 96(02): 220-227
DOI: 10.1160/TH06-02-0117

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Assessment of genetic risk for myocardial infarction

Authors

Yoshiji Yamada

¹Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Japan

²Gifu International Institute of Biotechnology, Kakamigahara, Japan
Hitoshi Matsuo

³Department of Cardiology, Gifu Prefectural Gifu Hospital, Gifu, Japan
Tomonori Segawa

³Department of Cardiology, Gifu Prefectural Gifu Hospital, Gifu, Japan
Sachiro Watanabe

³Department of Cardiology, Gifu Prefectural Gifu Hospital, Gifu, Japan
Kimihiko Kato

⁴Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan
Takeshi Hibino

⁴Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan
Kiyoshi Yokoi

⁴Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan
Sahoko Ichihara

¹Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Japan
Norifumi Metoki

⁵Department of Internal Medicine, Reimeikyo Rehabilitation Hospital, Minamitsugaru, Japan
Hidemi Yoshida

⁶Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan
Kei Satoh

⁶Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan
Yoshinori Nozawa

²Gifu International Institute of Biotechnology, Kakamigahara, Japan

Abstract

Summary

Although lifestyle and environmental factors influence the prevalence of myocardial infarction, genetic epidemiological studies have suggested that several genetic variants increase the risk for this condition. We have performeda large-scale association study to identify gene polymorphisms for reliable assessment of the genetic risk of myocardial infarction. The study population comprised 3,483 unrelated Japanese individuals (1,913 men; 1,570 women), including 1,192 subjects with myocardial infarction and 2,291 controls. The genotypes for 164 polymorphisms of 137 candidate genes were determined with an oligonucleotide ligation assay based on analysis of fluorescent microspheres with suspension array technology. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hypercholesterolemia revealed that the 677C→T (Ala222Val) polymorphism of MTHFR, the 1595C→G (Ser447Stop) polymorphism of LPL, and the –108/3G→4G polymorphism of IPF1 were significantly associated with the prevalence of myocardial infarction. A stepwise forward selection procedure demonstrated that IPF1, MTHFR, and LPL genotypes significantly affected the prevalence of myocardial infarction. Combined genotype analysis of these polymorphisms yieldeda maximum odds ratio of 2.54 for the combined genotype of TT for MTHFR,CC for LPL,and 3G3G for IPF1.The genotypes for MTHFR, LPL, and IPF1 may prove reliable for assessment of genetic risk for myocardial infarction. Determination of the combined genotype for these genes may contribute to primary, personalized prevention of this condition.

Keywords

Genetics - polymorphism - myocardial infarction - coronary heart disease - atherosclerosis

Full Text

References

References
1 Burke W. Genomics asa probe for disease biology. N Engl J Med 2003; 349: 969-74.
2 Thom T, Haase N, Rosamond W. et al. Heart disease and stroke statistics—2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2006; 113: e85-151.
3 Broeckel U, Hengstenberg C, Mayer B. et al. A comprehensive linkage analysis for myocardial infarction and its related risk factors. Nat Genet 2002; 30: 210-4.
4 Harrap SB, Zammit KS, Wong ZY. et al. Genomewide linkage analysis of the acute coronary syndrome suggests a locus on chromosome 2. Arterioscler Thromb Vasc Biol 2002; 22: 874-8.
5 Wang Q, Rao S, Shen GQ. et al. Premature myocardial infarction novel susceptibility locus on chromosome 1p34-36 identified by genomewide linkage analysis. Am J Hum Genet 2004; 74: 262-71.
6 Hauser ER, Crossman DC, Granger CB. et al. A genomewide scan for early-onset coronary artery disease in 438 families: the GENECARD Study. Am J Hum Genet 2004; 75: 436-47.
7 Cambien F, Poirier O, Lecerf L. et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992; 359: 641-4.
8 Weiss EJ, Bray PF, Tayback M. et al. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med 1996; 334: 1090-4.
9 Iacoviello L, Di Castelnuovo A, De Knijff P. et al. Polymorphisms in the coagulation factor VII gene and the risk of myocardial infarction. N Engl J Med 1998; 338: 79-85.
10 Kuivenhoven JA, Jukema JW, Zwinderman AH. et al. The role of a common variant of the cholesterol ester transfer protein gene in the progression of coronary atherosclerosis. N Engl J Med 1998; 338: 86-93.
11 Topol EJ, McCarthy J, Gabriel S. et al. Single nucleotide polymorphisms in multiple novel thrombospondin genes may be associated with familial premature myocardial infarction. Circulation 2001; 104: 2641-4.
12 Yamada Y, Izawa H, Ichihara S. et al. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med 2002; 347: 1916-23.
13 Ozaki K, Ohnishi Y, Iida A. et al. Functional SNPs in the lymphotoxin-a gene that are associated with susceptibility to myocardial infarction. Nat Genet 2002; 32: 650-4.
14 Ozaki K, Inoue K, Sato H. et al. Functional variation in LGALS2 confers risk of myocardial infarction and regulates lymphotoxin-α secretion in vitro . Nature 2004; 429: 72-5.
15 Shiffman D, Ellis SG, Rowland CM. et al. Identification of four gene variants associated with myocardial infarction. Am J Hum Genet 2005; 77: 596-605.
16 Itoh Y, Mizuki N, Shimada T. et al. High-throughput DNA typing of HLA-A, -B, -C, and -DRB1 loci by a PCR-SSOP-Luminex method in the Japanese population. Immunogenetics 2005; 57: 717-29.
17 Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc Ser B 1995; 57: 289-300.
18 Deloughery TG, Evans A, Sadeghi A. et al. Common mutation in methylenetetrahydrofolate reductase. Correlation with homocysteine metabolism and late-onset vascular disease. Circulation 1996; 94: 3074-8.
19 Ma J, Stampfer MJ, Hennekens CH. et al. Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US physicians. Circulation 1996; 94: 2410-6.
20 Schwartz SM, Siscovick DS, Malinow MR. et al. Myocardial infarction in young women in relation to plasma total homocysteine, folate, and a common variant in the methylenetetrahydrofolate reductase gene. Circulation 1997; 96: 412-7.
21 Kluijtmans LA, van den Heuvel LP, Boers GH. et al. Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am J Hum Genet 1996; 58: 35-41.
22 Gallagher PM, Meleady R, Shields DC. et al. Homocysteine and risk of premature coronary heart disease. Evidence fora common gene mutation. Circulation 1996; 94: 2154-8.
23 Morita H, Taguchi J, Kurihara H. et al. Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation 1997; 95: 2032-6.
24 Mager A, Lalezari S, Shohat T. et al. Methylenetetrahydrofolate reductase genotypes and early-onset coronary artery disease. Circulation 1999; 100: 2406-10.
25 Schmitz C, Lindpaintner K, Verhoef P. et al. Genetic polymorphism of methylenetetrahydrofolate reductase and myocardial infarction: a case-control study. Circulation 1996; 94: 1812-4.
26 Folsom AR, Nieto FJ, McGovern PG. et al. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 1998; 98: 204-10.
27 Verhoef P, Rimm EB, Hunter DJ. et al. A common mutation in the methylenetetrahydrofolate reductase gene and risk of coronary heart disease: results among U.S. men. J Am Coll Cardiol 1998; 32: 353-9.
28 Klerk M, Verhoef P, Clarke R. et al. MTHFR 677C→T polymorphism and risk of coronary heart disease: a meta-analysis. J Am Med Assoc 2002; 288: 2023-31.
29 Lewis SJ, Ebrahim S, Smith GD. Meta-analysis of MTHFR 677C→T polymorphism and coronary heart disease: Does totality of evidence support causal role for homocysteine and preventive potential of folate?. Br Med J 2005; 331: 1053-6.
30 Kastelein JJP, Jukema JW, Zwinderman AH. et al. Lipoprotein lipase activity is associated with severity of angina pectoris. Circulation 2000; 102: 1629-33.
31 Groenemeijer BE, Hallman MD, Reymer PWA. et al. Genetic variant showinga positive interaction with β-blocking agents with a beneficial influence on lipoprotein lipase activity, HDL cholesterol, and triglyceride levels in coronary artery disease patients. The Ser447-stop substitution in the lipoprotein lipase gene. Circulation 1997; 95: 2628-35.
32 Wittrup HH, Tybjærg-Hansen A, Nordestgaard BG. Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease. A metaanalysis. Circulation 1999; 99: 2901-7.
33 Ukkola O, Garenc C, Pérusse L. et al. Genetic variation at the lipoprotein lipase locus and plasma lipoprotein and insulin levels in the Que´bec Family Study. Atherosclerosis 2001; 158: 199-206.
34 Kuivenhoven JA, Groenemeyer BE, Boer JMA. et al. Ser447stop mutation in lipoprotein lipase is associated with elevated HDL cholesterol levels in normolipidemic males. Arterioscler Thromb Vasc Biol 1997; 17: 595-9.
35 Jemaa R, Fumeron F, Poirier O. et al. Lipoprotein lipase gene polymorphisms: associations with myocardial infarction and lipoprotein levels, the ECTIM study. J Lipid Res 1995; 36: 2141-6.
36 van Bockxmeer FM, Liu Q, Mamotte C. et al. Lipoprotein lipase D9N, N291S and S447X polymorphisms: their influence on premature coronary heart disease and plasma lipids. Atherosclerosis 2001; 157: 123-9.
37 Chen W, Srinivasan SR, Elkasabany A. et al. Influence of lipoprotein lipase serine 447 stop polymorphism on tracking of triglycerides and HDL cholesterol from childhood to adulthood and familial risk of coronary artery disease: the Bogalusa heart study. Atherosclerosis 2001; 159: 367-73.
38 Yang Y, Ruiz-Narvaez E, Niu T. et al. Genetic variants of the lipoprotein lipase gene and myocardial infarction in the Central Valley of Costa Rica. J Lipid Res 2004; 45: 2106-9.
39 Humphries SE, Nicaud V, Margalef J. et al. Lipoprotein lipase gene variation is associated with a paternal history of premature coronary artery disease and fasting and postprandial plasma triglycerides: the European Atherosclerosis Research Study (EARS). Arterioscler Thromb Vasc Biol 1998; 18: 526-34.
40 Henderson HE, Kastelein JJP, Zwinderman AH. et al. Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins. J Lipid Res 1999; 40: 735-43.
41 Zhang H, Henderson H, Gagne SE. et al. Common sequence variants of lipoprotein lipase: standardized studies of in vitro expression and catalytic function. Biochim Biophys Acta 1996; 1302: 159-66.
42 Ohlsson H, Karlsson K, Edlund T. IPF1, a homeodomain-containing transactivator of the insulin gene. EMBO J 1993; 12: 4251-9.
43 Inoue H, Riggs AC, Tanizawa Y. et al. Isolation, characterization, and chromosomal mapping of the human insulin promoter factor 1 (IPF-1) gene. Diabetes 1996; 45: 789-94.
44 Jonsson J, Carlsson L, Edlund T. et al. Insulin promoter-factor 1 is required for pancreas development in mice. Nature 1994; 371: 606-9.
45 Stoffers DA, Zinkin NT, Stanojevic V. et al. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat Genet 1997; 15: 106-10.
46 Yamada K, Yuan X, Ishiyama S. et al. Identification of a single nucleotide insertion polymorphism in the upstream region of the insulin promoter factor-1 gene: an association study with diabetes mellitus. Diabetologia 1998; 41: 603-5.
47 Hansen L, Urioste S, Petersen HV. et al. Missense mutations in the human insulin promoter factor-1 gene and their relation to maturity-onset diabetes of the young and late-onset type 2 diabetes mellitus in Caucasians. J Clin Endocrinol Metab 2000; 85: 1323-6.