Key result
The -519A→G polymorphism of MMP1 (OR 1.89) and the 1167C→T polymorphism of TGFBR2 (OR 0.62) were most significantly associated with chronic kidney disease in high- and low-risk individuals, respectively.
Why the study?
Which genetic polymorphisms are associated with susceptibility to chronic kidney disease in high- or low-risk Japanese subjects?
Case-Control (n=2,828)
Yes
Which genetic polymorphisms are associated with susceptibility to chronic kidney disease in high- or low-risk Japanese subjects?
Odds Ratio: 1.89 (95% CI 1.32–2.7)
p-value: p=0.0005
Genetic polymorphisms associated with chronic kidney disease susceptibility differ between individuals at high versus low conventional clinical risk, suggesting a role for risk-stratified genetic profiling.
The purpose of the present study was to identify genetic variants which confer susceptibility to chronic kidney disease (CKD) in high- or low-risk subjects defined by conventional risk factors separately. The study population comprised 2828 Japanese individuals, including 434 subjects with CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)] and 2394 controls (eGFR > or =60 ml/min/ 1.73 m(2)). The 1012 high-risk subjects had both hypertension and diabetes mellitus, and the 1816 low-risk subjects had none of these conditions. The genotypes for 296 polymorphisms of 202 candidate genes were determined. The Chi-square test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that ten different polymorphisms were associated (P<0.05) with the prevalence of CKD in high- or low-risk subjects: the -519Aright curved arrow G polymorphism of MMP1, the 1061Aright curved arrow G (Ile405Val) polymorphism of CETP, the Aright curved arrow G (Lys45Glu) polymorphism of MMP3, the -219Gright curved arrow T polymorphism of APOE, the Aright curved arrow G (Ile1205Val) polymorphism of COL3A1, the -863Cright curved arrow A polymorphism of TNF, and the 1454Cright curved arrow G (Leu125Val) polymorphism of PECAM1 in high-risk subjects; and the 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2, the 2386Aright curved arrow G (Ile796Val) polymorphism of SCAP, and the TAAAright curved arrow del polymorphism of PDE4D in low-risk subjects. Among these polymorphisms, the -519Aright curved arrow G polymorphism of MMP1 and the 1167Cright curved arrow T (Asn389Asn) polymorphism of TGFBR2 were most significantly associated with CKD in high- or low-risk individuals, respectively. These results suggest that polymorphisms associated with CKD may differ among high- or low-risk subjects. Stratification of subjects according to conventional risk factors may thus be important for personalized prevention of CKD based on genetic information.
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Yamada (2009) conducted a case-control in Chronic kidney disease (n=2,828). Gene polymorphisms (e.g., MMP1 -519A→G, TGFBR2 1167C→T) vs. Wild-type genotypes was evaluated on Prevalence of CKD in high-risk subjects (MMP1 -519A→G dominant model) (OR 1.89, 95% CI 1.32-2.70, p=0.0005). The -519A→G polymorphism of MMP1 (OR 1.89) and the 1167C→T polymorphism of TGFBR2 (OR 0.62) were most significantly associated with chronic kidney disease in high- and low-risk individuals, respectively.
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