Evaluation of the association between the common E469K polymorphism in the ICAM-1 gene and diabetic nephropathy among type 1 diabetic patients in GoKinD population.
BACKGROUND
The ICAM-1 gene is a strong positional and biological candidate for susceptibility to the development of T1D and DN. We have recently demonstrated that SNP rs5498(E469K) confers susceptibility to the development of T1D and might be associated with DN in Swedish Caucasians. The present study aimed to further evaluate the association between the ICAM-1 genetic polymorphisms and DN.


METHODS
Two common non-synonymous SNPs, including rs5498(E469K) and rs1799969(R241G), in the ICAM-1 gene were genotyped in 662 (312 female/350 male) T1D patients with DN and 620 (369/251) without DN. All patients were selected from the GoKinD study.


RESULTS
Genotype distributions of both SNPs were in Hardy-Weinberg equilibrium but SNP rs5498(E469K) had high heterozygous index. In this SNP, the heterozygosity and positivity for the allele G were found to be significantly associated with DN in female T1D patients (P = 0.010, OR = 0.633, CI 95% 0.447-0.895 and P = 0.026, OR = 0.692, CI 95% 0.500-0.958). Furthermore, the female patients without DN carrying three genotypes A/A, A/G and G/G had different cystatin levels (0.79 +/- 0.17, 0.81 +/- 0.14 and 0.75 +/- 0.12 mg/L, P = 0.021). No significant association of SNP rs1799969 (R241G) with DN was found.


CONCLUSIONS
The present study provides further evidence that SNP rs5498(E469K) in the ICAM-1 gene presents a high heterozygous index and the allele G of this polymorphism may confers the decreased risk susceptibility to the development of DN in female T1D patients among the GoKinD population.
Ma
Jun
J
Rolf Luft Center for Diabetes Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. jun.ma@ki.se
Zhang
Dongying
D
Brismar
Kerstin
K
Efendic
Suad
S
Gu
Harvest F
HF
D000328:Adult; D019943:Amino Acid Substitution; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D018799:Intercellular Adhesion Molecule-1