Gene-gene and gene-environment interactions: new insights into the prevention, detection and management of coronary artery disease

Table 3 Examples of replicated gene-gene and gene-environment interactions in CAD

Gene	Environment	Interaction	Independently associated with CAD?	References
LDLR	Lifestyle	Rare mutations have larger effect in less active people with high-fat diet	LDLR: yes; lifestyle: yes	[40, 42]
GSTM1, GSTT1	Smoking	Elevated CAD risk in smokers with null mutations	GSTM1, GSTT1: weak; smoking: yes	[47, 48]
APOE	Smoking	Exaggerated smoking-associated CAD risk in carriers of APOE ε4	APOE: yes; smoking: yes	[49, 50]
ADH1C	Alcohol consumption	Slow-metabolizing γ2 allele homozygotes have the greatest CAD protection	ADH1C: weak; alcohol: yes	[57, 58]
FGB	Strenuous exercise	Carriers of 455A allele have exaggerated increase in fibrinogen after exercise	FGB: no; exercise: yes	[51, 52]
F13A1	Plasma fibrinogen	Leu34 is protective for CAD in people with high fibrinogen levels	F13A1: no; fibrinogen: yes	[53, 54]
ACE, AGT		Unclear multi-locus epistatic interactions	ACE: no; AGT: no	[59, 60]
LPL, APOE		Greater negative effect of rare LPL alleles in APOE ε4 carriers	LPL: yes; APOE: yes	[55, 56]

Abbreviations: ACE, acetylcholine esterase; ADH1C, alcohol dehydrogenase 1C; AGT, angiotensinogen; APOE, apolipoprotein E; FGB, fibrinogen beta chain; F13A1, coagulation factor XIII, subunit A1; GSTM1, glutathione S-transferase mu 1; GSTT1, glutathione S-transferase theta 1; LDLR, low-density lipoprotein receptor; LPL, lipoprotein lipase.

ISSN: 1756-994X