A single nucleotide polymorphism in KCNQ1 is associated with susceptibility to diabetic nephropathy in japanese subjects with type 2 diabetes.
OBJECTIVE
Genetic factors have been considered to contribute to the development and progression of diabetic nephropathy. The KCNQ1 gene (potassium voltage-gated channel, KQT-like subfamily, member 1) was originally identified as a strong susceptibility gene for type 2 diabetes in two Japanese genome-wide association studies. In this study, we examined the association of single nucleotide polymorphisms (SNPs) within KCNQ1 with diabetic nephropathy in Japanese subjects with type 2 diabetes.


METHODS
We genotyped 33 SNPs in KCNQ1 using 754 type 2 diabetic patients with overt nephropathy and 558 control subjects (an initial study), and we further examined the association of a candidate SNP using three other independent Japanese populations (replications 1-3).


RESULTS
We found that five SNPs were nominally associated with diabetic nephropathy, and the association of rs2237897 was the strongest. We also found that the T allele frequencies of rs2237897 were consistently higher in the nephropathy groups than in the control groups for all study populations (initial study: 0.33 vs. 0.27; replication 1: 0.32 vs. 0.30; replication 2: 0.33 vs. 0.28; and replication 3: 0.32 vs. 0.28), although the individual associations did not reach statistically significant levels. Combined analysis by a meta-analysis revealed that the T allele of rs2237897 was significantly associated with susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes (odds ratio 1.22 [95% CI 1.10-1.34], P = 3.1 x 10(-4), corrected P = 0.01).


CONCLUSIONS
These results suggest that KCNQ1 is a new candidate gene for conferring susceptibility to diabetic nephropathy.
Ohshige
Toshihiko
T
Laboratory for Endocrinology andMetabolism, RIKEN Center for GenomicMedicine, Yokohama, Japan.
Tanaka
Yasushi
Y
Araki
Shin-ichi
S
Babazono
Tetsuya
T
Toyoda
Masao
M
Umezono
Tomoya
T
Watada
Hirotaka
H
Suzuki
Daisuke
D
Iwamoto
Yasuhiko
Y
Kawamori
Ryuzo
R
Nakamura
Yusuke
Y
Maeda
Shiro
S
D044466:Asian People / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D051657:KCNQ1 Potassium Channel