Developments in renal pharmacogenomics and applications in chronic kidney disease

Figures & data

Table 1 Characteristics and results of the main published studies involving gene polymorphisms and effect on renal function

Study	Population	N	Variable studied	SNPs	rs	Effect
Siddarth et al^Citation57	North Indian	334 cases (CKD patients), 334 controls (healthy patients)	Occurrence of CKD	CYP1A1*2A	rs4646903	C allele was associated with risk of CKD. TC OR =1.54 (P=0.013) and CC OR =2 (P=0.003)
				CYP1A1*2C	rs1048943	G allele was associated with risk of CKD. AG OR =1.67 (P=0.002) and GG OR =2.24 (P=0.004)
Kao et al^Citation137	African-American	1,372 cases (ESRD patients), 806 controls	Occurrence of CKD	MYH9	rs2032487	Diabetic patients: no association was observed Nondiabetic patients: C allele was associated with increased risk of ESRD (C OR =2.41, P=2.78×10^−8) Hypertensive patients: C allele was associated with increased risk of hypertensive ESRD (C OR =2.28, P=5.77×10^−7) FSGS patients: C allele was associated with increased risk of FSGS ESRD (C OR =4.85, P=6.14×10^−5)
					rs16996677	Diabetic: no association was observed Nondiabetic patients: A allele was associated with increased risk of ESRD (A OR =3.03, P=1.47×10^−7) Hypertensive patients: A allele was associated with increased risk of hypertensive ESRD (A OR =2.6, P=5.98×10^−5) FSGS patients: A allele was associated with increased risk of FSGS ESRD (A OR =5.38, P=8.07×10^−7)
					rs5756130	Diabetic patients: no association was observed Nondiabetic patients: C allele was associated with increased risk of ESRD (C OR =1.58, P=1×10^−3) Hypertensive patients: C allele was associated with increased risk of hypertensive ESRD (C OR =1.69, P=3.36×10^−3) FSGS patients: no association was observed
					rs5756129	Diabetic patients: no association was observed Nondiabetic patients: T allele was associated with increased risk of ESRD (T OR =1.71, P=3.21×10^−5) Hypertensive patients: T allele was associated with increased risk of hypertensive ESRD (T OR =1.62, P=2.04×10^−3) FSGS patients: T allele was associated with increased risk of FSGS ESRD (T OR =2.81, P=1.19×10^−3)
					rs4821481	Diabetic patients: no association was observed Nondiabetic patients: C allele was associated with increased risk of ESRD (C OR =2.40, P=2.8×10^−8) Hypertensive patients: C allele was associated with increased risk of hypertensive ESRD (C OR =2.32, P=4.37×10^−7) FSGS patients: C allele was associated with increased risk of FSGS ESRD (C OR =4.34, P=9.57×10^−5)
					rs3752462	Diabetic patients: no association was observed Nondiabetic patients: T allele was associated with increased risk of ESRD (T OR =2.11, P=1.98×10^−5) Hypertensive patients: no association was observed FSGS patients: T allele was associated with increased risk of FSGS ESRD (T OR =3.5, P=2.53×10^−3)
					rs5756152	Diabetic patients: no association was observed Nondiabetic patients: A allele was associated with increased risk of ESRD (A OR =2.59, P=2.25×10^−6) Hypertensive patients: A allele was associated with increased risk of hypertensive ESRD (A OR =2.54, P=1.59×10^−5) FSGS patients: A allele was associated with increased risk of FSGS ESRD (A OR =4.63, P=2.44×10^−6)
					rs1005570	Diabetic patients: no association was observed Nondiabetic patients: A allele was associated with increased risk of ESRD (A OR =2.56, P=4.33×10^−9) Hypertensive patients: A allele was associated with increased risk of hypertensive ESRD (A OR =2.07, P=3.54×10^−5) FSGS patients: A allele was associated with increased risk of FSGS ESRD (A OR =4.49, P=3.63×10^−7)
					rs16996674	Diabetic patients: no association was observed Nondiabetic patients: T allele was associated with increased risk of ESRD (T OR =3.1, P=4.14×10^−7) Hypertensive patients: T allele was associated with increased risk of hypertensive ESRD (T OR =2.78, P=3.56×10^−5) FSGS patients: T allele was associated with increased risk of FSGS ESRD (T OR =6.84, P=6.82×10^−9)
Matsha et al^Citation140	People of African ancestry	716 chosen from the general population	Renal function: estimated GFR calculated with the MDRD formula	MYH9	rs5756152	Diabetic patients: G allele was associated with increased renal function (+11 mL/min/1.73 m^2, P=0.0002) Nondiabetic patients: no association was observed
					rs12107	No association was observed
Tavira et al^Citation141	Spanish	592 chosen from the general population	Renal function: estimated GFR calculated with the MDRD formula	MYH9	rs3752462 T	T allele was associated with GFR <60 mL/min/1.73 m^2 (P=0.003)
					rs4821480 T	G allele was more frequent in GFR <60 mL/min/1.73 m^2 (P=0.16)
Cooke et al^Citation139	European American	536 cases (type 2 diabetes mellitus ESRD patients), 467 controls (type 2 diabetes mellitus patients), 960 controls (healthy patients)	Occurrence of type 2 diabetes mellitus ESRD	MYH9	rs4821480	Versus diabetic nonP: G allele had a trend of association with ESRD (OR =6.14, P=0.0.53). Versus nondiabetic nonP: G allele had a trend of association with ESRD (OR =2.5, P=0.107) Versus controls (diabetic and nondiabetic): G allele was associated with ESRD (OR =3.11, P=0.033)
					rs2032487	Versus diabetic nonP: G allele had a trend of association with ESRD (OR =6.09, P=0.054) Versus nondiabetic nonP: G allele had a trend of association with ESRD (OR =3.13, P=0.056) Versus controls (diabetic and nondiabetic): G allele was associated with ESRD (OR =3.72, P=0.017)
					rs4281481	Versus diabetic nonP: G allele had a trend of association with ESRD (OR =6.08, P=0.055) Versus nondiabetic nonP: G allele had a trend of association with ESRD (OR =3.11, P=0.058) Versus controls (diabetic and nondiabetic): G allele was associated with ESRD (OR =3.70, P=0.017)
				APOL1	rs375462	No statistical analysis due to the low frequency in European Americans
Parsa et al^Citation182	African-American (AASK study)	693	Composite renal outcome: doubling of serum creatinine level from baseline or incident ESRD.	APOL1	rs73885319 rs60910145 rs71785313	Patients with two copies of APOL1 variants had an increased risk of composite renal outcome: OR =2.03, P<0.001 Patients with one copy of APOL1 variants: no association was observed
	African- and European Americans (CRIC study)	2,955				Diabetic patients: black patients in the APOL1 high-risk and low-risk groups, compared with white patients, had an increased risk of composite renal outcome: OR =1.95, P<0.001 and OR =1.4, P=0.006, respectively. Nondiabetic patients: black patients in the APOL1 high-risk and low-risk groups, compared with white patients, had an increased risk of composite renal outcome: OR =2.68, P,0.001 and OR =1.57, P=0.01, respectively
Yang et al^Citation122	Chinese	630 cases (ESRD patients), 415 controls (healthy patients)	Occurrence of ESRD	TLR-9	rs5743836	C allele was associated with increased risk of ESRD (C OR =4.36, P=0.001)
					rs187084	C allele was associated with reduced risk of ESRD (C OR =0.71, P=0.05)
					rs352140	No association was observed
Jimenez-Sousa et al^Citation123	Spanish	276 cases (kidney transplant patients), 288 controls (healthy patients)	Occurrence of ESRD	IL4R	rs1801275	AG genotype was associated with reduced risk of ESRD. (AG OR =0.66, P=0.025)
				STAT4 binding site	rs301640	A genotype was associated with increased risk of ESRD (A OR =1.82, P=0.0064)
				CCL2	rs4586	C genotype was associated with reduced risk of ESRD (C OR =0.7, P=0.0051)
				NOS3	rs7830	T genotype was associated with increased risk of ESRD (T OR =1.31, P=0.043)
Singh et al^Citation124	North Indian	200 cases (ESRD patients), 200 controls (healthy patients)	Development of ESRD	CXCL12G801A	rs1801157	GA genotype was associated with ESRD risk (OR =1.55, P=0.039)
				CXCR2	rs1801032	CT genotype was associated with ESRD risk (OR =1.65, P=0.02)
				CCLI/D	rs3917887	DD genotype showed a reduced risk of ESRD (OR =0.45, P=0.035)
				CCL2A518G	rs1024611	No association was observed
Nabrdalik et al^Citation125	Caucasian	109 cases (CKD patients of at least stage 3), 111 controls (healthy patients)	Occurrence of CKD Progression of CKD: mean reduction of GFR per year (calculated with MDRD). Hypertension appearance	TGFβ1	rs1800471	Occurrence of CKD: C allele was related with higher risk of CKD (OR =2.0, P=0.035) Progression of CKD: no association was observed Hypertension occurrence: G genotype was associated with risk of hypertension (OR =5.9, P=0.0021)
Silva et al^Citation133	Brazilian	106 hypertensive patients treated with enalapril	Response to enalapril in hypertensive patients	eNOS		Good responders showed higher frequencies of the TC and CC genotypes TC OR =0.35, P=0.0005 and CC OR =0.38, P=0.0424
				BDKRB2		Poor responders showed higher frequencies of TT genotypes. TT OR =3.06, P=0.0106

Notes: G1 risk allele: presence of rs73885319 and rs60910145. G2 risk allele: presence of rs71785313 APOL1 risk: defined according to the number of copies of the risk alleles. Zero or one copy = low risk. Two copies = high risk

Abbreviations: APOL1, apolipoprotein L1; CKD, chronic kidney disease; eNOS, nitric oxide synthase; (endothelial) ESRD, end-stage renal disease; FSGS, focal segmental glomerulosclerosis; GFR, glomerular filtration rate; MDRD, Modification of Diet in Renal Disease; nonP, non-nephropathy; OR, odds ratio; SNPs, single-nucleotide polymorphisms; TGFβ1, transforming growth factor beta 1; BDKRB2, bradykinin receptor B2; AASK, African American Study of Kidney Disease and Hypertension; CRIC, Chronic Renal Insufficiency Cohort.

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KaoWHKlagMJMeoniLAMYH9 is associated with nondiabetic end-stage renal disease in African AmericansNat Genet200840101185119218794854

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MatshaTEMasconiKYakoYYPolymorphisms in the non-muscle myosin heavy chain gene (MYH9) are associated with lower glomerular filtration rate in mixed ancestry diabetic subjects from South AfricaPLoS One2012712e5252923285077

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TaviraBCotoEGómezJAssociation between a MYH9 polymorphism (rs3752462) and renal function in the Spanish RENASTUR cohortGene20135201737623470845

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CookeJNBostromMAHicksPJPolymorphisms in MYH9 are associated with diabetic nephropathy in European AmericansNephrol Dial Transplant20122741505151121968013

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ParsaAKaoWHXieDAPOL1 risk variants, race, and progression of chronic kidney diseaseN Engl J Med2013369232183219624206458

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YangHYLuKCLeeHSRole of the functional Toll-Like receptor-9 promoter polymorphism (−1237T/C) in increased risk of end-stage renal disease: a case-control studyPLoS One201383e5844423472199

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SinghVJaiswalPKTiwariPKapoorRMittalRDAssociation of chemokine gene variants with end stage renal disease in North Indian populationTranspl Immunol201328418919223615182

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