Table 1.

Genetic factors associated with ICAS.

Gene	Gene function	Polymorphism	Study population	Sample size	Main finding	References
ADIPOQ	Regulate adiponectin level	g.15734A>G	Chinese	602 (199 ICAS / 403 controls)	Increased risk of ICAS	[36]
			American	2847	Related to carotid and coronary atherosclerosis in African Americans	[35]
			Chinese	2212 (1105 T2DM /1107 controls)	Closely related to hypoadiponectinemia	[42]
		g.5320G>A	American	1200 (600 MI or IS / 600 controls)	Reduced of cerebral infarction risk level	[37]
			Chinese	476	Elevated plasma adrenomedullin levels	[43]
RNF213	Result in vascular fragility, lead to vessels more vulnerable to hemodynamic stress	c.14576G>A	Japanese	433	Significant association with ICAS	[47]
			Japanese	221	Associated with anterior ICAS	[48]
		c.14429G>A	Korean	532	Associated with vasculogenesis	[53]
APOE	Associate with high LDL cholesterol level	ɛ4	Finnish	700	Associated with larger coronary and aortic atherosclerotic lesion areas in men	[58]
			American	720		[59]
			Finnish	536 (237 IS / 362 controls)	There was a link with ICAS in men	[60]
			Thai	308	Associated with extracranial atherosclerosis	[61]
PDE4D	Has a major role in the degradation of cAMP	g.319027C>T	Indian	336	TT genotype was associated with ICAS	[72]
MTHFR	Reduce enzyme activity, decrease folate level and increase Hcy	g.14783C>T	Chinese	929	This variant and Hcy had interaction in the formation of cerebral atherosclerosis	[78]
			Korean	463 (267 atherosclerosis / 196 controls)	Hcy level and this variant did not contribute to the distribution of cerebral atherosclerosis	[79]
LPL	Involve in plasma lipoprotein metabolism and transportation	g.27496T>G	Indian	1025 (525 IS / 500 controls)	Associated with intracranial large artery atherosclerosis	[81]
		p.Ser447Stop	Japanese	354 (177 CVD / 177 controls)	Reduced risk of atherothrombotic cerebral infarction	[80]
		g.23608C>T, p.Ser447Ter	Chinese	371 (185 CI / 186 controls)	Closely associated with atherothrombotic cerebral infarction	[82]
ADD1	Associate with blood pressure levels	p.Gly460Trp	Dutch	6471 and 1018	Associated with atherosclerosis	[88]
			Indian	339	No significant difference between ICAS and extracranial atherosclerosis	[89]
ACE	Take part in vascular remodeling and the development of atherosclerosis	Insertion/Deletion	Thai	308	No association between this polymorphism and ICAS	[61]
			Chinese	210		[94]
			Chinese	708		[95]
CYP11B2	Involve in the aldosterone system	g.4660T>C	Indian	797 (403 stroke / 394 controls)	Associated with intracranial large artery atherosclerosis	[98]

CI: cerebral infarction; CVD: cerebrovascular disease; ICAS: intracranial atherosclerosis; IS: ischemic stroke; MI: myocardial infarction; T2DM: type 2 diabetes mellitus.