Other entities represented in this entry:
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1p32.3 | {Myocardial infarction, susceptibility to} | 608446 | 3 | LRP8 | 602600 | |
| 1p22.1 | {Myocardial infarction, susceptibility to} | 608446 | 3 | GCLM | 601176 | |
| 1q25.1 | {Myocardial infarction, susceptibility to} | 608446 | 3 | TNFSF4 | 603594 | |
| 6p25.1 | {Myocardial infarction, protection against} | 608446 | 3 | F13A1 | 134570 | |
| 6p21.33 | {Myocardial infarction, susceptibility to} | 608446 | 3 | LTA | 153440 | |
| 6p12.1 | {Myocardial infarction, susceptibility to} | 608446 | 3 | GCLC | 606857 | |
| 6q25.1-q25.2 | {Myocardial infarction, susceptibility to} | 608446 | 3 | ESR1 | 133430 | |
| 12p13.2 | {Myocardial infarction, susceptibility to} | 608446 | 3 | OLR1 | 602601 | |
| 13q34 | {Myocardial infarction, decreased susceptibility to} | 608446 | 3 | F7 | 613878 | |
| 14q13.2 | {Myocardial infarction, susceptibility to} | 608446 | 3 | PSMA6 | 602855 | |
| 17q21.32 | {Myocardial infarction, susceptibility to} | 608446 | 3 | ITGB3 | 173470 | |
| 22q12.1 | {Myocardial infarction, susceptibility to} | 608446 | 3 | MIAT | 611082 | |
| 22q13.1 | {Myocardial infarction, susceptibility to} | 608446 | 3 | LGALS2 | 150571 |
A number sign (#) is used with this entry because evidence suggests that susceptibility to myocardial infarction (MI) can be conferred by variation in several genes. These genes include ESR1 (133430) on chromosome 6q25; LGALS2 (150571) on 22q13; LTA (153440) on 6p21; ITGB3 (173470) on 17q21; THBD (188040) on 20p11; GCLM (601176) on 1p22; OLR1 (602601) on 12p13; PSMA6 (602855) on 14q13; GCLC (606857) on 6p12; and MIAT (611082) on 22q12.
Variation in the LRP8 gene (602600) on chromosome 1p34 defines the MCI1 locus; another locus for myocardial infarction, MCI2 (608557), has been mapped to chromosome 13q12-q13.
Protection against myocardial infarction has been associated with variation in the F13A1 gene (134570) on 6p25 and the F7 gene (613878) on 13q34.
The most frequent causes of death and disability in the Western world are atherosclerotic coronary artery disease (CAD; see 608320) and acute myocardial infarction (MI).
Wang et al. (2004) reported results of a genomewide search for susceptibility genes for MI in a well-characterized U.S. cohort consisting of 1,613 individuals in 428 multiplex families with familial premature CAD and MI: 712 with MI, 974 with CAD, and average age of onset of 44.4 +/- 9.7 years. A single novel significant susceptibility locus for MI was identified on 1p36-p34, with a multipoint allele-sharing P value of less than 10(-12), i.e., lod = 11.68. For the less restrictive phenotype of CAD, no genetic locus was detected, suggesting that CAD and MI may not share all susceptibility genes.
Shen et al. (2007) analyzed candidate genes in the 1p36-p34 region, including the LRP8 gene (602600) which encodes apolipoprotein E receptor-2. A nonconservative substitution, R952Q (602600.0001), was significantly associated with susceptibility to premature coronary artery disease and/or myocardial infarction by use of both population-based and family-based designs. The association was significantly replicated in 2 independent populations. The R952Q variant of LRP8 increased activation of p38 mitogen-activated protein kinase (MAPK14; 600289) by oxidized low density lipoprotein.
Shen, G.-Q., Li, L., Girelli, D., Seidelmann, S. B., Rao, S., Fan, C., Park, J. E., Xi, Q., Li, J., Hu, Y., Olivieri, O., Marchant, K., and 9 others. An LRP8 variant associated with familial and premature coronary artery disease and myocardial infarction. Am. J. Hum. Genet. 81: 780-791, 2007. [PubMed: 17847002] [Full Text: https://doi.org/10.1086/521581]
Wang, Q., Rao, S., Shen, G.-Q., Li, L., Moliterno, D. J., Newby, L. K., Rogers, W. J., Cannata, R., Zirzow, E., Elston, R. C., Topol, E. J. Premature myocardial infarction novel susceptibility locus on chromosome 1p34-36 identified by genomewide linkage analysis. Am. J. Hum. Genet. 74: 262-271, 2004. Note: Erratum: Am. J. Hum. Genet. 74: 1080 only, 2004. [PubMed: 14732905] [Full Text: https://doi.org/10.1086/381560]