Genetic influences of the intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms in development of Type 1 diabetes and diabetic nephropathy

• Published in: Diabetic medicine Vol. 23; no. 10; pp. 1093 - 1099
• Main Authors: Ma, J., Möllsten, A., Prázny, M., Falhammar, H., Brismar, K., Dahlquist, G., Efendic, S., Gu, H. F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2006; Blackwell
• Subjects: Adult; Biological and medical sciences; Diabetes; Diabetes Mellitus, Type 1 - genetics; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - genetics; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; genetic association; Genetic Predisposition to Disease - genetics; genetics; Humans; Intercellular Adhesion Molecule-1 - genetics; intercellular adhesion molecule 1; Male; Medical sciences; Middle Aged; nephropathy; Original; Polymorphism, Genetic - genetics; single nucleotide polymorphism; Sweden; Type 1; Type 1 diabetes mellitus; Sweden; Endocrinopathy; Kidney disease; Immunopathology; Urinary system disease; Genetic variability; Intercellular adhesion molecule 1; Cell adhesion molecule; genetic association; Autoimmune disease; Genotype; Nephropathy; Type 1 diabetes; Genetics; Single nucleotide polymorphism; Type 1 diabetes mellitus
• ISSN: 0742-3071; 1464-5491; 1464-5491
• DOI: 10.1111/j.1464-5491.2006.01948.x

Aim  The intercellular adhesion molecule‐1 (ICAM‐1) gene is located on chromosome 19p13, which is linked to Type 1 diabetes (T1D). ICAM‐1 expression is related to development of T1D and diabetic nephropathy. The present study aims to evaluate the genetic influence of ICAM‐1 gene polymorphisms on the development of T1D and diabetic nephropathy. Methods  Five valid single nucleotide polymorphisms (SNPs) were genotyped in 432 T1D patients (196 patients had diabetic nephropathy) and 187 non‐diabetic control subjects by using dynamic allele‐specific hybridization (DASH) and pyrosequencing. Results  SNPs rs281432(C/G) and rs5498 E469K(A/G) had high heterozygous indexes. They were significantly associated with T1D [P = 0.026, OR = 1.644 (95% CI 1.138–2.376) and P < 0.001, OR = 2.456 (1.588–3.8)]. Frequencies of the C allele in SNP rs281432(C/G) and the A allele in SNP rs5498 E469K(A/G) increased stepwise from non‐diabetic control subjects to T1D patients without diabetic nephropathy and T1D patients with diabetic nephropathy. Further analysis for these two SNPs indicated that T1D patients had increased frequency of the common haplotype C‐A, in comparison with non‐diabetic control subjects (38.1 vs. 32.1%, P = 0.035). Conclusion  The present study provided evidence that SNPs rs281432(C/G) and rs5498 E469K(A/G) in the ICAM‐1 gene confer susceptibility to the development of T1D and might also be associated with diabetic nephropathy in Swedish Caucasians.