Table 3.

Association between ACE/ ACE2 polymorphisms and human disorders in different populations.

Gene	SNP	Disease	Treatment	Case/Control	Population	Conclusion	Reference
ACE	ACE I/D	Kidney Disease and Hypertension	ACE inhibitor ramipril	347	African American	II or DD homozygous genotypes and homozygous ACE haplotypes confer faster response to Ramipril.	[61]
		Hypertension	ACEI Enalapril, Lisinopril or Imidapril	190 (70 with cough /120 without cough)	Japanese	ACE-inhibitor-induced cough was not related to the ACE polymorphism.	[62]
		ACEI-induced cough	ACE inhibitor	144/105	Spanish	The rs4646994 I allele is associated with cough (protective effect in males and risk conferring in females).	[63]
		Erectile dysfunction	Sildenafil	113/118	German	ACE II homozygous patients are better responder to sildenafil.	[64]
		hypertrophic cardiomyopathy (HCM)	–	368 MYPBC3 mutation carriers	Dutch	ACE-DD was significantly associated with the Wigle score.	[65]
		Post exercise CK increase	–	70 Healthy athletes	Ashkenazi and non-Ashkenazi Caucasian	ACE II/ID was associated with elevated CK activity and higher peak CK levels.	[66]
		Psoriasis	–	207/ 182	Austrian Caucasian	ACE II genotype was associated with higher risk of early-onset psoriasis.	[67]
		cardiometabolic disease	Chlorthalidone, calcium channel blocker (amlodipine) or ACEi (lisinopril)	9309/ 8164	–	ACE I/D polymorphism was associated with fasting glucose level during antihypertensive treatment.	[68]
		Heart failure (HF)	–	58	Canadian Caucasian	AGT (T235)/ACE(D) combined polymorphisms associated with HF predisposition	[69]
		Pneumonia	–	1239/2400	Asian Caucasian	ACE-DD genotype of rs4340 polymorphism is associated with increased risk of pneumonia	[70]
		Multiple sclerosis (MS)	IFN-β1a treatment	391/ 380	Persian	Higher prevalence of ACE I allele in MS patients, overrepresentation of the I allele in irresponsive patients to IFN-β.	[71]
		Healthy persons	–	80	Caucasians	ACE I allele is associated with higher serum level of ACE.	[72]
ACE 2	rs1978124 (A1075G)	Hypertension	Anti-hypertensive (F/M %) 16.05/ 12.59	1009/756	Chinese Han	Significant haplotype: G-T-G-G-A (rs1978124, rs2106809, rs1403543, rs5194, rs56204867)	[73]
		Retinopathy T2DM	–	743 cases DR/DNR F: 237/171 M:182/153	Chinese	rs2074192 (TT) and rs714205 (CC) were higher in DR in female (P < .05).	[74]
	rs879922	T2 Diabetes	–	275/272	Uygurs	The rs1978124, rs2048683, rs2074192, rs233575, rs4240157, rs4646156, rs4646188 and rs879922 were associated with T2D. The rs879922 is common maker for T2D and related cardiovascular risks.	[75]
	rs2106809	hypertrophic cardiomyopathy	–	261/ 609	Chinese Han	T allele of rs2106809 and C allele of rs6632677 conferred risk for HCM.	[76]
		Hypertension	ACEI Benazepril/ Imidapril	497 hypertensive patients	Chinese Han	Lower BP in CC/CT carrier female	[77]
			–	246/274	Odisha, India	ACE (DD) and rs2106809 (TT) were associated with disease in females.	[78]
			Atenolol, Hydrochlorothiazide, Captopril, or Nifedipine	3408 untreated hypertensive patients	Chinese Han	T allele confers a high risk for hypertension and reduced antihypertensive response to ACE inhibitors.	[79]
		AF	–	265/289	Chinese Han	rs2106809 (T) conferred higher risk of AF in males.	[80]
	rs2074192	Hypertension	–	647 cases 289 LVH/ 358	Chinese Han	ACE2 tag SNPs rs2074192 and rs2106809 as well as major haplotypes CCGC and TCGT are associated with blood pressure and LVH.	[81]
	rs4646176	Blood pressure	High/low-sodium intervention	1906 cases from 637 families	Chinese Han	rs1514283, rs1514282, and rs4646176 were significantly associated with SBP, DBP, or MAP responses to low and high-sodium intervention.	[82]
	rs2285666 (G8790A)	fatal CAD events	–	1382 CAD/ 453 fatal CAD	Finnish, Swedish, Irish, French	rs2285666 (A) significantly associated with the risk of cardiovascular death in female.	[83]
		hypertension T2 Diabetes with stroke	–	7251 cases	Han Chinese	G8790A is a risk factor for hypertension in Han-Chinese males, and females from other ethnicities.	[84]