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.

Lanktree and Hegele Genome Medicine 2009 1:28   doi:10.1186/gm28