J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://jocmr.elmerjournals.com

Original Article

Volume 18, Number 10, October 2026, pages 721-727

Klotho Gene Single-Nucleotide Polymorphism and Proteinuria in a General Population

↓ Figure 1. Possible mechanistical linking proteinuria, disordered phosphate metabolism, and cardiovascular risk. Proteinuria downregulates renal Klotho expression, impairing FGF23 signaling and NaPi-IIa degradation in the proximal tubule. This leads to reduced urinary phosphate excretion, phosphate retention, and vascular toxicity, thereby linking albuminuria to cardiovascular risk and progressive renal dysfunction. Solid arrows indicate established relationships, whereas dashed arrows indicate modulatory or proposed relationships. FGF23: fibroblast growth factor 23; NaPi-IIa: sodium-dependent phosphate cotransporter IIa.

↓ **Table 1.** Characteristics According to the Klotho Gene rs650439 SNP Alleles
Variable	All (n = 916)	AA + AT (n = 795)	TT (n = 121)	P-value
Values are shown as the mean ± standard deviation for continuous variables and as numbers (%) for categorical variables. Genotypes were coded as TT versus AA + AT. Student’s t-test was used for continuous variables, whereas the chi-square test was used for categorical variables. An asterisk (*) indicates statistical significance (P < 0.05). BMI: body mass index; eGFR: estimated glomerular filtration rate.
Age, years	63 ± 14	63 ± 14	65 ± 12	0.13
Male, n (%)	415 (45.3%)	357 (44.9%)	58 (47.9%)	0.60
Alcohol consumption, n (%)	437 (47.7%)	378 (47.5%)	59 (48.8%)	0.88
Current smoking, n (%)	327 (35.7%)	285 (35.8%)	42 (34.7%)	0.89
BMI, kg/m²	22.9 ± 3.2	22.8 ± 3.3	23.2 ± 3.1	0.59
Total cholesterol, mg/dL	205.9 ± 35.0	206.3 ± 35.0	203.7 ± 35.3	0.75
Creatinine, mg/dL	0.74 ± 0.19	0.73 ± 0.18	0.78 ± 0.23	0.04*
eGFR, mL/min/1.73 m²	74.9 ± 15.3	75.2 ± 15.0	72.5 ± 16.7	0.19
eGFR, < 60 mL/min/1.73 m²	168 (18.3%)	136 (17.1%)	32 (26.4%)	0.02*
Hypertension, n (%)	385 (42.0%)	328 (41.3%)	57 (47.1%)	0.26
Diabetes mellitus, n (%)	92 (10.0%)	79 (9.9%)	13 (10.7%)	0.91
Proteinuria, n (%)	77 (8.4%)	58 (7.3%)	19 (15.7%)	< 0.01*

↓ Table 1. Characteristics According to the Klotho Gene rs650439 SNP Alleles

Variable

All (n = 916)

AA + AT (n = 795)

TT (n = 121)

P-value

Values are shown as the mean ± standard deviation for continuous variables and as numbers (%) for categorical variables. Genotypes were coded as TT versus AA + AT. Student’s t-test was used for continuous variables, whereas the chi-square test was used for categorical variables. An asterisk (*) indicates statistical significance (P < 0.05). BMI: body mass index; eGFR: estimated glomerular filtration rate.

Age, years

63 ± 14

65 ± 12

0.13

Male, n (%)

415 (45.3%)

357 (44.9%)

58 (47.9%)

0.60

Alcohol consumption, n (%)

437 (47.7%)

378 (47.5%)

59 (48.8%)

0.88

Current smoking, n (%)

327 (35.7%)

285 (35.8%)

42 (34.7%)

0.89

BMI, kg/m²

22.9 ± 3.2

22.8 ± 3.3

23.2 ± 3.1

0.59

Total cholesterol, mg/dL

205.9 ± 35.0

206.3 ± 35.0

203.7 ± 35.3

0.75

Creatinine, mg/dL

0.74 ± 0.19

0.73 ± 0.18

0.78 ± 0.23

0.04*

eGFR, mL/min/1.73 m²

74.9 ± 15.3

75.2 ± 15.0

72.5 ± 16.7

0.19

eGFR, < 60 mL/min/1.73 m²

168 (18.3%)

136 (17.1%)

32 (26.4%)

0.02*

Hypertension, n (%)

385 (42.0%)

328 (41.3%)

57 (47.1%)

0.26

Diabetes mellitus, n (%)

92 (10.0%)

79 (9.9%)

13 (10.7%)

0.91

Proteinuria, n (%)

77 (8.4%)

58 (7.3%)

19 (15.7%)

< 0.01*

↓ **Table 2.** Univariate and Multivariate Logistic Regression Analysis of Proteinuria
Variable	Crude OR (95% CI)	P-value	Adjusted OR (95% CI) of model 1	P-value	Adjusted OR (95% CI) of model 2	P-value
Crude odds ratios (ORs) were calculated using univariate logistic regression of proteinuria with TT genotype. Adjusted ORs were calculated using multivariate logistic regression of proteinuria with TT genotype in model 1 (to which age, sex, eGFR, hypertension, diabetes mellitus, and genotypes were entered) and model 2 (to which age, sex, alcohol consumption, smoking, BMI, total cholesterol, eGFR, hypertension, diabetes mellitus, and genotypes were entered). Genotypes were coded as TT versus AA + AT. An asterisk (*) indicates statistical significance (P < 0.05). BMI: body mass index; eGFR: estimated glomerular filtration rate.
Age, years	1.03 (1.01–1.05)	< 0.01*	1.01 (0.99–1.03)	0.32	1.01 (0.99–1.03)	0.37
Male	2.05 (1.27–3.30)	< 0.01*	1.83 (1.11–3.02)	0.02*	1.47 (0.75–2.88)	0.26
Alcohol consumption	1.27 (0.80–2.03)	0.31	-	-	1.15 (0.66–2.01)	0.62
Current smoking	1.56 (0.98–2.50)	0.06	-	-	1.13 (0.60–2.15)	0.71
BMI, kg/m²	1.03 (0.97–1.10)	0.30	-	-	1.00 (0.93–1.08)	0.95
Total cholesterol, mg/dL	0.99 (0.98–1.00)	0.01*	-	-	0.99 (0.99–1.00)	0.06
eGFR, mL/min/1.73 m²	0.97 (0.96–0.99)	< 0.01*	0.98 (0.96–1.00)	0.01*	0.98 (0.96–0.99)	0.01*
Hypertension	2.97 (1.81–4.85)	< 0.01*	2.07 (1.21–3.55)	< 0.01*	2.02 (1.16–3.50)	0.01*
Diabetes mellitus	4.39 (2.53–7.63)	< 0.01*	3.29 (1.82–5.94)	< 0.01*	3.28 (1.80–5.97)	< 0.01*
TT genotype (vs. AA + AT)	2.37 (1.35–4.14)	< 0.01*	2.08 (1.15–3.77)	0.02*	2.07 (1.14–3.77)	0.02*

↓ Table 2. Univariate and Multivariate Logistic Regression Analysis of Proteinuria

Variable

Crude OR (95% CI)

P-value

Adjusted OR (95% CI) of model 1

P-value

Adjusted OR (95% CI) of model 2

P-value

Crude odds ratios (ORs) were calculated using univariate logistic regression of proteinuria with TT genotype. Adjusted ORs were calculated using multivariate logistic regression of proteinuria with TT genotype in model 1 (to which age, sex, eGFR, hypertension, diabetes mellitus, and genotypes were entered) and model 2 (to which age, sex, alcohol consumption, smoking, BMI, total cholesterol, eGFR, hypertension, diabetes mellitus, and genotypes were entered). Genotypes were coded as TT versus AA + AT. An asterisk (*) indicates statistical significance (P < 0.05). BMI: body mass index; eGFR: estimated glomerular filtration rate.

Age, years

1.03 (1.01–1.05)

< 0.01*

1.01 (0.99–1.03)

0.32

1.01 (0.99–1.03)

0.37

Male

2.05 (1.27–3.30)

< 0.01*

1.83 (1.11–3.02)

0.02*

1.47 (0.75–2.88)

0.26

Alcohol consumption

1.27 (0.80–2.03)

0.31

1.15 (0.66–2.01)

0.62

Current smoking

1.56 (0.98–2.50)

0.06

1.13 (0.60–2.15)

0.71

BMI, kg/m²

1.03 (0.97–1.10)

0.30

1.00 (0.93–1.08)

0.95

Total cholesterol, mg/dL

0.99 (0.98–1.00)

0.01*

0.99 (0.99–1.00)

0.06

eGFR, mL/min/1.73 m²

0.97 (0.96–0.99)

< 0.01*

0.98 (0.96–1.00)

0.01*

0.98 (0.96–0.99)

0.01*

Hypertension

2.97 (1.81–4.85)

< 0.01*

2.07 (1.21–3.55)

< 0.01*

2.02 (1.16–3.50)

0.01*

Diabetes mellitus

4.39 (2.53–7.63)

< 0.01*

3.29 (1.82–5.94)

< 0.01*

3.28 (1.80–5.97)

< 0.01*

TT genotype (vs. AA + AT)

2.37 (1.35–4.14)

< 0.01*

2.08 (1.15–3.77)

0.02*

2.07 (1.14–3.77)

0.02*