Table 2.

Gene–gene interactions as risk factors for white matter lesions (WMLs)

Gene 1	Gene 2	P/OR	N	Sample	Reference
Methylenetetrahydrofolate reductase (MTHFR) 677TT	APOE E4/E4 + E4/E3	P < 0.005; OR = 2.47	315/646	Leukoaraiosis/Control	[117]a
MTHFR 677TT	APOE E2/E2 + E2/E3	P < 0.0005; OR = 2.52	315/646	Leukoaraiosis/Control	[117]a
MTHFR 677TT	Angiotensin I‐converting enzyme(ACE)D/D	P < 0.0005; OR = 4.90	229/362	Leukoaraiosis/Control	[115]a
Apolipoprotein E (APOE) E2 allele	ACE D/D	P < 0.05; OR = 2.11	315/646	Leukoaraiosis/Control	[117]a
Angiotensinogen (AGT) M235T	ACE D allele	P < 0.01; OR = 11.70	93/583	Cerebral Infarction/Control	[116]b,c
Angiotensinogen (AGT) M235T	APOE E4 allele	NS	93/583	Cerebral Infarction/Control	[116]b
AGT M235T ACE I/D AGTR1 A1166C NOS3 G894T	No interaction between these polymorphisms	NS	93	Hypertensive subjects	[107]
AGT M235T AGTR1 A1166C ACE I/D	No interaction between these polymorphisms	NS	60	Hypertensive subjects	[106]

^aUnclear if control samples were in Hardy–Weinberg equilibrium.

^bNon‐Caucasian population.

^cGenotype frequencies for the ACE control group were not in Hardy–Weinberg equilibrium.