Heart disease

Heart disease, in SNPedia as well as for the entry in Wikipedia, is a catch-all term including medical classifications such as coronary artery disease, myocardial infarction, atherosclerosis, etc. Heart disease overall is the #1 cause of death in developed countries, typically accounting for up to 40% of all deaths.

Many SNPs have been associated with increased risk for one or more types of heart disease. Before listing many of them, though, it is worth emphasizing that the risks associated with these SNPs add "relatively little to the current capacity of traditional, non-genetic risk factors to identify individuals with a high propensity to develop heart disease"[1]. This is generally true of most SNPs associated with other diseases as well.

SNPs and genes associated with altered risk for heart disease include the following:

• The most highly replicated associations to heart disease have been to SNPs in the chromosome 9p21 region. SNPs in this region include:
  • rs2383206
  • rs10757278
  • rs2383207
  • rs10757274

• rs4665058 is associated with a 2x higher risk of sudden cardiac death, based on a GWAS study and subsequent follow up studies in European ancestry populations

• 7 new loci (with one or more SNPs per locus) associated with heart disease, or HDL/LDL cholesterol levels, that are generally quite common and generally of relatively small effect each [overview article; 10.1038/ng.76; 10.1038/ng.2007.61; 10.1038/ng.75

• The 7 SNPs found recently (2007) by the Wellcome Trust Case Control Consortium to be associated with risk for coronary artery disease [PMID 17554300], namely:
  • rs1333049
  • rs17672135
  • rs383830
  • rs6922269
  • rs8055236
  • rs7250581
  • rs688034
  • rs2943634 is a SNP found in both the Wellcome report and then independently in the German MI (Myocardial infarction) Family study [PMID 17634449]

• The 4 additional SNPs found after pooling the Wellcome and German MI data together [PMID 17634449], namely:
  • rs599839
  • rs17465637
  • rs501120
  • rs17228212

• rs10757274 and rs2383206 can double the risk of heart disease. About one in every four Caucasians are thought to carry the gene variants.
• rs10757278 in the same region has been linked to diabetes [2]

• rs2713604 and rs3803 are identified as associated with Familial Early-Onset Coronary Artery Disease Gene variants reveal susceptibility to cardiovascular disease is the press release for this research paper.

• ALOX5AP haplotypes are associated with risk for myocardial infarction and stroke in some European population but not others.

• The Klf15 transcription factor involved in circadian rhythm may affect susceptibility to sudden cardiac death and aortic aneurysm. Nature letter Science article.

• [PMID 18320357]: 4 SNP haplotype of HSPD1 gene defining 2x CHD risk based on study of 1,000 Chinese patients; see rs788016

• [PMID 17101857] the AA genotype of the triallelic SNP rs3091244 in the gene C-reactive protein was associated with prevalent coronary heart disease in the non-Hispanic white population

• rs1800787 (T;T) homozygotes are at 6 fold higher risk for carotid atherosclerosis [PMID 9514419]. This polymorphism is known as the "C148-T" variant, and is located in at the "-148" position of the FGB gene, also known as beta fibrinogen.

• rs5082 (C;C) homozygotes have a lower CHD risk

• [PMID 16278826] Cryptic haplotypes of SERPINA1 confer susceptibility to chronic obstructive pulmonary disease

• [PMID 16979000] A SNP in NOS3 predicts cardiovascular mortality in high-risk patients

• [PMID 16957409] KLOTHO G395A polymorphism was associated with blood pressure and KLOTHO C1818T polymorphism was associated with glucose metabolism

• rs662799 and rs3135506 are two SNPs in APOA5 reported to modulate the effects (and thus the risk) of a high fat diet on BMI and risk of heart disease

• [PMID 18318786] 'Novel alternative transcript' haplotype (rs1676232 and rs4404477, among others, identify the haplotype) of LSAMP associated with risk of late-onset left main coronary artery disease

Myocardial infarction (heart attack) is specifically mentioned in these reports:

• [PMID 16845397] A functional SNP in PSMA6 confers risk of myocardial infarction in the Japanese population

• [PMID 17211523] A functional SNP in ITIH3 is associated with susceptibility to myocardial infarction.

• [PMID 17066261] rs2331291 a non-coding RNA, MIAT, that confers risk of myocardial infarction.

• [PMID 17893005] Two MMP9 SNPs, rs3918242 and rs17576, are associated with MI but not CAD in a study of 5,000+ patients.

( Rs708272, the TaqIB area of CETP has been associated with HDL and CAD.

Several studies have also reported finding no associations with SNPs previously published to be associated with certain heart diseases, including:

• [PMID 17426274] Our null results provide no support for the hypothesis that any of the 85 genetic variants tested is a susceptibility factor for acute coronary syndromes.