To validate the Selleck SCH727965 association between SIRT1 and diabetic nephropathy, we examined another 195 cases (overt proteinuria) and 264 controls registered in the BioBank Japan (study 4). As shown in Table 7, most SNPs showed a consistent Saracatinib solubility dmso association with those in the original finding, and the association of the haplotype was strengthened further (P = 0.0028, OR 1.36, 95% CI 1.11–1.66). We further examined the association between SIRT1 SNPs and microalbuminuria in studies 1 and 2, but could not identify a significant

association (Supplementary Table 3), suggesting SIRT1 SNPs might contribute to the progression of nephropathy rather than its onset in patients with type 2 diabetes.

Table 1 Association between SNPs in SIRT1 and diabetic nephropathy   Allele frequencies (nephropathy case−control) Proteinuria ESRD Combined Study 1 Study 2 P OR (95% CI) Study 3 P OR (95% CI) SNP  rs12778366a T>C 0.111/0.103 0.125/0.124 0.672 1.04 (0.86–1.26) 0.101/0.119 0.981 0.998 (0.84–1.18)  rs3740051a A>G 0.291/0.277 0.316/0.301 0.299 1.07 (0.94–1.22) 0.310/0.274 0.138 1.09 (0.97–1.23)  rs2236318a T>A 0.121/0.129 0.099/0.111 0.327 0.91 (0.75–1.10) 0.106/0.119 0.236 0.90 (0.76–1.07)  rs2236319 ABT-263 cell line A>G 0.339/0.317 0.358/0.339 0.165 1.09 (0.96–1.24) 0.349/0.300 0.048 1.12 (1.00–1.26)  rs10823108 G>A 0.335/0.318 0.357/0.335 0.169 1.09 (0.96–1.24) 0.351/0.302 0.049 1.12 (1.00–1.26)  rs10997868a C>A 0.187/0.184 0.187/0.174 0.520 1.05 (0.90–1.23) 0.180/0.173 0.482 1.05 (0.91–1.21)  rs2273773 T>C 0.339/0.325 0.361/0.347 0.325 1.07 (0.94–1.21) 0.353/0.306 0.113 1.10 (0.98–1.23)  rs3818292 A>G 0.336/0.317

0.360/0.335 0.134 1.10 (0.97–1.25) 0.352/0.306 0.042 1.13 (1.00–1.26)  rs3818291 G>A 0.111/0.101 0.127/0.129 0.650 1.04 (0.87–1.26) 0.101/0.124 0.927 0.99 (0.84–1.17)  rs4746720a T>C 0.366/0.394 0.331/0.364 0.041 0.88 (0.77–0.99) 0.367/0.400 0.021 0.88 (0.78–0.98)  rs10823116a A>G 0.446/0.442 0.441/0.448 0.905 0.99 (0.88–1.12) 0.459/0.394 0.428 1.05 (0.94–1.16) Haplotype  TGTGACCGGTG 0.294/0.279 GBA3 0.316/0.300 0.250 1.08 (0.95–1.23) 0.315/0.273 0.095 1.10 (0.98–1.24)  TATAGCTAGCA 0.255/0.273 0.251/0.252 0.464 0.95 (0.83–1.09) 0.253/0.304 0.143 0.91 (0.81–1.03)  CATAGCTAATA 0.112/0.103 0.124/0.129 0.817 1.02 (0.85–1.23) 0.100/0.119 0.841 0.98 (0.83–1.16)  TAAAGATAGTA 0.123/0.128 0.104/0.112 0.484 0.94 (0.78–1.13) 0.105/0.122 0.319 0.92 (0.78–1.08)  TATAGCTAGCG 0.109/0.123 0.085/0.111 0.037 0.81 (0.67–0.99) 0.113/0.099 0.117 0.87 (0.73–1.03)  TATAGATAGTA 0.065/0.055 0.078/0.059 0.051 1.27 (0.998–1.61) 0.077/0.053 0.016 1.31 (1.05–1.62)  TATGACCGGTG 0.042/0.039 0.040/0.036 0.57 1.09 (0.81–1.48) 0.036/0.028 0.421 1.12 (0.85–1.48) aTag SNPs Fig.