22) 0.044 1.12 (1.00–1.24) Acalabrutinib rs10823108 G>A 0.358/0.337 0.127 1.09 (0.97–1.23) 0.038 1.12 (1.01–1.24) rs10997868a C>A 0.181/0.175 0.490 1.05 (0.91–1.21) 0.456 1.05 (0.92–1.20) rs2273773 T>C 0.364/0.342 0.239 1.07 (0.95–1.20) 0.085 1.10 (0.99–1.22) rs3818292 A>G
0.358/0.344 0.120 1.10 (0.98–1.23) 0.040 1.12 (1.01–1.24) rs3818291 G>A 0.090/0.132 0.696 0.97 (0.81–1.15) 0.412 0.94 (0.80–1.10) rs4746720a T>C 0.371/0.361 0.084 0.90 (0.81–1.01) 0.044 0.90 (0.81–0.997) rs10823116a A>G 0.453/0.450 0.939 0.996 (0.89–1.11) 0.446 1.04 (0.94–1.15) Haplotype TGTGACCGGTG 0.306/0.297 0.240 1.07 (0.95–1.21) 0.098 1.09 (0.98–1.22) TATAGCTAGCA 0.269/0.243 0.809 0.96 (0.87–1.11) 0.336 0.95 (0.85–1.06) CATAGCTAATA 0.105/0.129 0.741 0.97 (0.82–1.15) 0.496 0.95 (0.81–1.10) TAAAGATAGTA 0.122/0.116 0.621 0.96 (0.81–1.13) 0.430 0.94 (0.80–1.09) TATAGCTAGCG 0.095/0.112 0.022 0.82 (0.69–0.97) 0.071 0.86 (0.74–1.01) TATAGATAGTA 0.072/0.059 0.0091 1.34 (1.07–1.66) 0.0028 1.36 (1.11–1.66) TATGACCGGTG 0.031/0.044 0.942 1.01 (0.77–1.33) 0.746 1.04 (0.81–1.35) aTag
SNPs Discussion In the present study, we identified that SNPs within SIRT1 were nominally associated with susceptibility to diabetic nephropathy. SIRT1 encodes a member of NAD(+)-dependent histone deacetylase, involved in various nuclear events such as transcription, DNA replication, and DNA repair. Cumulative evidence ATM Kinase Inhibitor clinical trial during the past decade has demonstrated that SIRT1 plays an important role not only in the regulation of aging and longevity, but also in the development and/or progression of age-associated metabolic diseases, such as type 2 diabetes. SIRT1 activation is considered to be a key mediator for favorable effects on lifespan or on metabolic activity in animals under Galactosylceramidase calorie restriction (CR)
[21–24]. Recently, Kume et al. [19] reported that mice under 40% CR were protected from the development of glomerular sclerosis in aging mice kidneys through increasing mitochondrial biogenesis caused by sirt1 activation. From these observations, it is suggested that SIRT1 has a pivotal role in the pathogenesis of aging-related metabolic diseases, such as type 2 VX-765 nmr diabetes or glomerulosclerosis, and a genetic difference in SIRT1 activity among individuals, if it is present, may contribute to conferring susceptibility to these diseases. In the present study, we identified that SNPs within SIRT1 were nominally associated with diabetic nephropathy, whereas SNPs in other sirtuin families did not show any association with diabetic nephropathy.
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