Genetic association study of TERT gene variants with chronic kidney disease susceptibility in the Chinese population

Figures & data

Table 1. Characteristics of patients with chronic kidney disease and healthy individuals.

Characteristics	Cases, n = 507	Control, n = 510	p
Age (years, mean ± SD)	49.40 ± 16.76	49.40 ± 16.09	0.999
> 50	265 (52%)	267 (52%)
≤ 50	242 (48%)	243 (48%)
Gender			0.941
Male	312 (62%)	315 (62%)
Female	195 (38%)	195 (38%)
MAU (mg/L)	616.22 ± 845.45	29.81 ± 30.09	< 0.001
UA (umol/L)	402.57 ± 135.45	331.37 ± 90.07	< 0.001
Creatinine (umol/L)	409.39 ± 443.26	66.18 ± 13.83	< 0.001
Urea (mmol/L)	13.88 ± 19.06	4.92 ± 1.26	< 0.001
CKD stage
CKD1	154	–	–
CKD2	100	–	–
CKD3	45	–	–
CKD4	22	–	–
CKD5	164	–	–
Missing	22	–	–

MAU: microalbuminuria; UA: uric acid; CKD: chronic kidney disease

p < 0.05 and bold text indicates statistical significance.

Figure 1. Comparisons of the genotype frequency and allele frequency of SNPs in the TERT gene between the CKD case and healthy control groups. (a–d) Comparisons of the genotype frequencies of rs2736100, rs2853677, rs2735940, and rs4635969. (e–h) Comparisons of the allele frequencies of rs2736100, rs2853677, rs2735940, and rs4635969. ‘*’ indicates statistical significance at the 0.05 level.

Table 2. The basic information and HWE about the selected SNPs.

Gene	SNP ID	Chrs	Position	Function	Alleles (A/B)	MAF		HWE (p value)	Haploreg 4.2
						Cases	Control
TERT	rs2736100	5	1286401	intronic	C/A	0.442	0.446	0.531	Motifs changed, NHGRI/EBI GWAS hits, GRASP QTL hits
TERT	rs2853677	5	1287079	intronic	G/A	0.402	0.374	0.850	NHGRI/EBI GWAS hits
TERT	rs2735940	5	1296371	–	A/G	0.546	0.478	1.000	Promoter histone marks, Enhancer histone marks
TERT	rs4635969	5	1308437	–	A/G	0.147	0.106	0.638	Enhancer histone marks, Motifs changed, NHGRI/EBI GWAS hits

HWE: Hardy–Weinberg equilibrium; SNP: single nucleotide polymorphisms; Chrs: chromosome number; Alleles (A/B): minor/major allele; MAF: minor allele frequency

p > 0.05 indicates that the genotypes were in Hardy–Weinberg Equilibrium.

Figure 2. Analysis of the association between susceptibility to CKD and SNPs. SNPs: single nucleotide polymorphisms; OR: odds ratio; CI: confidence interval; p values represent adjustment for age and gender; p < 0.05, bold text and ‘*’ indicate statistical significance.

Table 3. The SNPs associated with susceptibility to chronic kidney disease in the subgroup tests (age and gender).

SNP ID	Model	Genotype	Age				Gender
			≤ 50 (N = 485)	p	> 50 (N = 532)	p	Male (N = 627)	p	Female (N = 390)	p
			OR (95% CI)		OR (95% CI)		OR (95% CI)		OR (95% CI)
rs2736100	Allele	C	0.91 (0.71–1.17)	0.468	1.05 (0.83–1.34)	0.681	0.96 (0.77–1.20)	0.718	1.02 (0.77–1.36)	0.893
		A	1		1		1		1
	Codominant	CA	0.90 (0.60–1.36)	0.614	1.06 (0.72–1.57)	0.754	1.01 (0.71–1.46)	0.942	0.94 (0.60–1.46)	0.770
		CC	0.83 (0.50–1.38)	0.484	1.11 (0.68–1.81)	0.673	0.92 (0.59–1.42)	0.695	1.08 (0.60–1.94)	0.805
		AA	1		1		1		1
	Dominant	CA-CC	0.88 (0.60–1.29)	0.513	1.08 (0.75–1.56)	0.690	0.98 (0.70–1.38)	0.915	0.97 (0.63–1.48)	0.890
		AA	1		1		1		1
	Recessive	CC	0.89 (0.57–1.38)	0.602	1.07 (0.70–1.64)	0.757	0.91 (0.62–1.33)	0.621	1.12 (0.67–1.89)	0.667
		AA-CA	1		1		1		1
	Log-additive	–	0.91 (0.71–1.17)	0.471	1.06 (0.83–1.34)	0.663	0.96 (0.77–1.20)	0.725	1.02 (0.77–1.36)	0.886
rs2853677	Allele	G	1.09 (0.84–1.41)	0.518	1.15 (0.90–1.48)	0.254	1.15 (0.91–1.44)	0.244	1.09 (0.81–1.46)	0.566
		A	1		1		1		1
	Codominant	GA	1.11 (0.75–1.63)	0.605	1.24 (0.85–1.80)	0.267	1.29 (0.91–1.82)	0.152	1.01 (0.66–1.56)	0.962
		GG	1.19 (0.67–2.11)	0.548	1.30 (0.77–2.19)	0.320	1.23 (0.76–1.98)	0.394	1.28 (0.67–2.44)	0.458
		AA	1		1		1		1
	Dominant	GA-GG	1.13 (0.78–1.63)	0.532	1.25 (0.88–1.79)	0.215	1.27 (0.92–1.76)	0.147	1.06 (0.70–1.60)	0.780
		AA	1		1		1		1
	Recessive	GG	1.12 (0.66–1.90)	0.663	1.15 (0.72–1.85)	0.556	1.07 (0.69–1.65)	0.770	1.27 (0.70–2.31)	0.433
		AA-GA	1		1		1		1
	Log-additive	–	1.10 (0.84–1.43)	0.502	1.16 (0.91–1.49)	0.240	1.15 (0.91–1.44)	0.243	1.10 (0.81–1.48)	0.549
rs2735940	Allele	A	1.29 (1.00–1.67)	0.046*	1.32 (1.04–1.69)	0.023*	1.27 (1.02–1.59)	0.035*	1.38 (1.04–1.82)	0.026*
		G	1		1		1		1
	Codominant	AG	1.37 (0.88–2.12)	0.164	1.53 (0.99–2.38)	0.058	1.57 (1.05–2.33)	0.027*	1.27 (0.77–2.09)	0.343
		AA	1.68 (1.00–2.81)	0.048*	1.82 (1.11–2.99)	0.018*	1.64 (1.05–2.56)	0.031*	1.98 (1.10–3.56)	0.023*
		GG	1		1		1		1
	Dominant	AG-AA	1.46 (0.96–2.21)	0.075	1.63 (1.07–2.47)	0.023*	1.59 (1.09–2.32)	0.015*	1.46 (0.91–2.34)	0.120
		GG	1		1		1		1
	Recessive	AA	1.36 (0.90–.08)	0.149	1.35 (0.92–1.98)	0.126	1.20 (0.85–1.72)	0.304	1.67 (1.04–2.68)	0.033*
		GG-AG	1		1		1		1
	Log-additive	–	1.30 (1.00–1.68)	0.048*	1.34 (1.05–1.71)	0.020*	1.27 (1.02–1.59)	0.036*	1.41 (1.05–1.89)	0.023*
rs4635969	Allele	A	1.62 (1.09–2.40)	0.016*	1.33 (0.93–1.91)	0.113	1.61 (1.14–2.28)	0.006*	1.25 (0.83–1.89)	0.292
		G	1		1		1		1
	Codominant	AG	1.49 (0.95–2.33)	0.084	1.34 (0.90–2.00)	0.151	1.55 (1.05–2.27)	0.027*	1.20 (0.75–1.93)	0.439
		AA	3.86 (0.79–18.82)	0.095	2.21 (0.40–12.24)	0.363	3.94 (0.81–19.17)	0.089	2.12 (0.38–11.77)	0.391
		GG	1		1		1		1
	Dominant	AG-AA	1.59 (1.03–2.46)	0.036*	1.37 (0.92–2.03)	0.117	1.63 (1.12–2.37)	0.012*	1.24 (0.79–1.97)	0.351
		GG	1		1		1		1
	Recessive	AA	3.56 (0.73–17.34)	0.116	2.06 (0.37–11.35)	0.408	3.60 (0.74–17.45)	0.112	2.03 (0.37–11.22)	0.419
		GG-AG	1		1		1		1
	Log-additive	–	1.59 (1.08–2.36)	0.020*	1.36 (0.94–1.97)	0.099	1.62 (1.15–2.30)	0.006*	1.26 (0.83–1.91)	0.288

SNP: single nucleotide polymorphisms; OR: odds ratio; CI: confidence interval

p < 0.05, bold text and ‘*’ indicate statistical significance.

Figure 3. Dendrogram of SNP-SNP interactions. The colors in the tree diagram represent either synergy or redundancy.

Table 4. SNP–SNP interaction models analyzed by the MDR method.

Model	Training Bal. Acc	Testing Bal. Acc	p Value	CVC
rs2735940	0.540	0.519	0.0038	8/10
rs2735940, rs4635969	0.564	0.559	p < 0.0001	10/10
rs2736100, rs2735940, rs4635969	0.570	0.516	p < 0.0001	9/10
rs2736100, rs2853677, rs2735940, rs4635969	0.581	0.524	p < 0.0001	10/10

MDR: multifactor dimensionality reduction; Bal. Acc.: balanced accuracy; CVC: cross-validation consistency.

p values were calculated using χ² tests; p < 0.05 and bold text indicate statistical significance.

Table 5. Clinical characteristics of patients (N = 507) based on the genotypes of selected SNPs.

	MAU	UA	Creatinine	Urea
rs2736100
AA	684.24 ± 1044.44	412.99 ± 136.42	383.46 ± 388.40	13.62 ± 9.00
CA	578.15 ± 680.48	399.34 ± 131.05	441.32 ± 509.88	12.94 ± 8.25
CC	579.42 ± 779.71	395.58 ± 144.64	370.46 ± 342.56	16.41 ± 39.23
p	0.575	0.522	0.290	0.320
rs2853677
AA	655.17 ± 930.86	415.64 ± 134.65	387.62 ± 395.33	13.11 ± 8.56
GA	604.39 ± 806.75	395.87 ± 138.49	431.73 ± 498.38	13.01 ± 8.39
GG	566.20 ± 742.23	398.66 ± 124.20	380.01 ± 343.46	18.76 ± 45.05
p	0.798	0.332	0.512	0.064
rs2735940
AA	577.18 ± 878.21	397.08 ± 128.38	397.47 ± 553.65	15.83 ± 33.37
GA	532.39 ± 638.66	405.81 ± 135.13	419.43 ± 393.34	12.88 ± 8.10
GG	870.10 ± 1148.92	405.07 ± 146.16	398.70 ± 390.69	13.85 ± 9.12
p	0.023*	0.822	0.868	0.348
rs4635969
AA	668.19 ± 370.72	360.27 ± 117.26	365.64 ± 411.09	9.65 ± 6.22
GA	603.59 ± 837.23	394.65 ± 138.18	395.23 ± 361.02	13.67 ± 8.77
GG	618.97 ± 860.88	406.74 ± 134.99	415.80 ± 470.80	14.09 ± 21.82
p	0.977	0.401	0.858	0.742

MAU: microalbuminuria; UA: uric acid

p < 0.05, bold text and ‘*’ represent statistical significance.

Data availability statement

The original contributions or analyzed during this study are available from the article. Further inquiries can be made to the corresponding author.