KCNQ1 SNPS and susceptibility to diabetic nephropathy in East Asians with type 2 diabetes.
OBJECTIVE
A Japanese study had earlier reported that KCNQ1 single-nucleotide polymorphisms (SNPs) may be associated with diabetic nephropathy. To further investigate this finding, we analysed three SNPs, rs2237895, rs2237897 and rs2283228, within the KCNQ1 locus for association with albuminuria among Chinese type 2 diabetic patients residing in Singapore. Albuminuria was analysed as both categorical (micro- and macroalbuminuria) and continuous traits (log(e) albumin/creatinine ratio [ACR]).


METHODS
A total of 752 Chinese patients with type 2 diabetes were included in the study. Albuminuria was determined by ACR using spot urine samples, and renal function was approximated using estimated GFR. Genotyping was performed using invader and Taqman assays as appropriate. Multivariate regression analyses were used to analyse the associations between SNPs and renal traits.


RESULTS
Significant associations were detected between rs2283228 and macroalbuminuria (p < 0.001, corrected p < 0.01), as well as log(e) ACR (p = 0.004, corrected p = 0.036) after multiple hypothesis testing and adjustment for potential confounding. A trend of increasing OR was observed with increasing severity of diabetic nephropathy (low and high microalbuminuria, macroalbuminuria). rs2237897, previously implicated in the earlier Japanese study, was also associated with macroalbuminuria, but this finding did not remain significant after correction for multiple testing. Meta-analyses of the Chinese and Japanese studies revealed both SNPs to be significantly associated with macroalbuminuria.


CONCLUSIONS
Together with the previous Japanese study, our findings support the hypothesis that, in addition to KCNQ1 being an established type 2 diabetes gene, genetic variation in this gene may contribute to susceptibility to diabetic nephropathy in East Asians.
Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive MD3, 117597 Singapore, Republic of Singapore.
X L
XL
Lim
S
S
Nurbaya
A
A
Salim
E S
ES
Tai
S
S
Maeda
Y
Y
Nakamura
D P K
DP
Ng
D000368:Aged; D000419:Albuminuria / Q000453:epidemiology / Q000235:genetics* / Q000652:urine; D044466:Asian People / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism*; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics* / Q000652:urine; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000235:genetics* / Q000652:urine; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012846:Singapore / Q000453:epidemiology
D001786:Blood Glucose; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D003404:Creatinine