Diabetic kidney disease: Are the reported associations with single-nucleotide polymorphisms disease-specific?

doi:10.4239/wjd.v12.i10.1765

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World Journal of Diabetes

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Case Control Study

World J Diabetes. Oct 15, 2021; 12(10): 1765-1777
Published online Oct 15, 2021. doi: 10.4239/wjd.v12.i10.1765

Table 1 Study and control group characteristics

	DKD (n = 117)	NDKD (n = 110)	P value
Age (yr)	68.94 (7.90)	69.87 (10.86)	0.46
Male sex (%)	57 (48.72)	66 (60.00)	0.088
Time-to-dialysis (yr)	5.25 (5.16)	6.23 (6.09)	0.20
Rapid progression of CKD (TTD ≤ 3 mo) (%)	6 (5.13)	6 (5.45)	0.91
Fast progression of CKD (TTD ≤ 1 yr) (%)	29 (24.79)	21 (19.09)	0.30
Slow progression of CKD (TTD > 5 yr) (%)	37 (31.62)	43 (39.09)	0.24
BMI (kg/m²)	30.21 (16.35)	26.01 (5.15)	0.01
Smoking ever (%)	52 (44.44)	58 (53.21)¹	0.19
Preserved diuresis (%)	97 (82.91)	85 (77.27)	0.29
24 h diuresis > 500 mL (%)	49 (41.88)	46(41.82)	0.99
Hypertension (%)	114 (97.44)	102 (92.73)	0.099
ACE-I (%)	50 (43.48)²	39 (39.39)⁴	0.54
ARB (%)	17 (14.78)²	12 (11.76)⁵	0.51
Beta-blockers (%)	89 (76.72)³	91 (89.22)⁵	0.015
Statins (%)	76 (66.09)²	57 (58.16)⁶	0.23

¹Data available for 109 patients.

²Data available for 115 patients.

³Data available for 116 patients.

⁴Data available for 99 patients.

⁵Data available for 102 patients.

⁶Data available for 98 patients.

Significant differences are highlighted in bold. ACE-I: Angiotensin-converting-enzyme inhibitors; ARB: Angiotensin II receptor blockers; BMI: Body mass index; CKD: Chronic kidney disease; DKD: Diabetic kidney disease; NDN: Non-diabetic kidney disease; TTD: Time-to-dialysis (time between the diagnosis of chronic kidney disease and start of hemodialysis).

Table 2 Single-nucleotide polymorphisms’ associations with diabetic kidney disease

SNP	DKD		NDKD		OR	P value
SNP	E	N	E	N	OR	P value
rs1617640	123	111	119	101	0.94 (0.65-1.36)	0.78
rs841853	84	150	60	160	1.49 (1.00-2.23)	0.048
rs1800783	67	167	69	151	0.88 (0.59-1.31)	0.53
rs1531343	23	211	17	203	1.30 (0.68-2.51)	0.43
rs1800470	91	143	93	127	0.87 (0.60-1.26)	0.46
rs759853	94	140	74	146	1.32 (0.90-1.94)	0.15
rs1801282	40	194	35	185	1.06 (0.66-1.79)	0.73
rs13293564	104	130	91	129	1.13 (0.78-1.65)	0.51
rs2268388	29	205	32	188	0.83 (0.48-1.43)	0.50

DKD: Diabetic kidney disease; E: Effect allele; NDKD: Non-diabetic kidney disease; N: Non-effect allele; OR: Odds ratio; SNP: Single nucleotide polymorphism.

Table 3 Associations between genetic risk score and different parameters in diabetic kidney disease and non-diabetic kidney disease patients

Parameter	DKD + NDKD, n = 227		DKD, n = 117		NDKD¹, n = 91
Parameter	GRS, mean ± SD	P value	GRS, mean ± SD	P value	GRS, mean ± SD	P value
Rapid progression (TTD ≤ 3 mo vs > 3 mo)	0.602 ± 0.233 vs 0.603 ± 0.258	0.99	0.518 ± 0.273 vs 0.620 ± 0.260	0.34	0.687 ± 0.167 vs 0.574 ± 0.248	0.27
Fast progression (TTD ≤ 1 yr vs > 1 yr)	0.592 ± 0.246 vs 0.606 ± 0.260	0.75	0.600 ± 0.229 vs 0.620 ± 0.270	0.71	0.522 ± 0.253 vs 0.593 ± 0.242	0.30
Slow progression (TTD > 5 yr vs ≤ 5 yr)	0.596 ± 0.256 vs 0.607 ± 0.258	0.77	0.629 ± 0.286 vs 0.608 ± 0.249	0.69	0.583 ± 0.230 vs 0.580 ± 0.257	0.96
Diuresis (preserved diuresis vs no diuresis)	0.614 ± 0.260 vs 0.557 ± 0.239	0.18	0.622 ± 0.265 vs 0.578 ± 0.235	0.49	0.605 ± 0.244 vs 0.503 ± 0.235	0.09
24h diuresis > 500 mL (> 500 mL vs ≤ 500 mL)	0.630 ± 0.244 vs 0.583 ± 0.265	0.17	0.621 ± 0.258 vs 0.611 ± 0.263	0.83	0.643 ± 0.220 vs 0.535 ± 0.253	0.035
Male sex (males vs females)	0.639 ± 0.265 vs 0.591 ± 0.255	0.31	0.617 ± 0.263 vs 0.586 ± 0.249	0.37	0.589 ± 0.251 vs 0.568 ± 0.235	0.70

¹Cases with complex pathogenesis excluded from analysis.

DKD: Diabetic kidney disease; NDKD: Non-diabetic kidney disease; GRS: Genetic risk score; TTD: Time-to-dialysis (time between the diagnosis of chronic kidney disease and start of hemodialysis). Significant differences are highlighted in bold.

Table 4 The distribution of genetic risk score in particular end-stage kidney disease subgroups

Group	GRS	P value	Post-hoc analysis
Classification: (1) GD, (2) TID, (3) VD, (4) CCD, (5) CP
		0.09	GD vs TID	P = 0.014
			GD vs VD	P = 0.12
GD (n = 146)	0.628 ± 0.256		GD vs CCD	P = 0.61
TID (n = 16)	0.461 ± 0.218		GD vs CP	P = 0.97
VD (n = 33)	0.551 ± 0.269		TID vs VD	P = 0.24
CCD (n = 13)	0.590 ± 0.138		TID vs CCD	P = 0.18
CP (n = 19)	0.629 ± 0.298		TID vs CP	P = 0.051
			VD vs CCD	P = 0.64
			VD vs CP	P = 0.29
			CCD vs CP	P = 0.66
Classification: (1) GD, (2) TID+VD+CCD, (3) CP
GD (n = 146)	0.628 ± 0.256	0.055	GD vs TID+VD+CCD	P = 0.018
TID+VD+CCD (n = 62)	0.536 ± 0.235		GD vs CP	P = 0.97
CP (n = 19)	0.629 ± 0.298		TID+VD+CCD vs CP	P = 0.16
Classification: (1) GD, (2) TID+VD+CCD+CP
GD	0.628 ± 0.256	0.051	N/A
TID+VD+CCD+CP	0.558 ± 0.253	0.051	N/A

Genetic risk score is presented as mean ± SD. GRS: Genetic risk score; GD: Glomerular disease; TID: Tubulointerstitial disease; VD: Vascular diseases; CCD: Cystic and congenital disease; CP: Complex pathogenesis; N/A: Not applicable.

Citation: Saracyn M, Kisiel B, Franaszczyk M, Brodowska-Kania D, Żmudzki W, Małecki R, Niemczyk L, Dyrla P, Kamiński G, Płoski R, Niemczyk S. Diabetic kidney disease: Are the reported associations with single-nucleotide polymorphisms disease-specific? World J Diabetes 2021; 12(10): 1765-1777
URL: https://www.wjgnet.com/1948-9358/full/v12/i10/1765.htm
DOI: https://dx.doi.org/10.4239/wjd.v12.i10.1765