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Genetic variation in receptor protein tyrosine phosphatase is associated with type 2 diabetes in Swedish Caucasians

Department of Molecular Medicine and Surgery, Karolinska Institutet, Rolf Luft Center for Diabetes Research, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden

(Correspondence should be addressed to E-C Långberg; Email: ewa-carin.langberg{at}ki.se)

Objective: Previously, it has been demonstrated that receptor protein tyrosine phosphatase (RPTP) is involved in glucose homeostasis and insulin signaling in several animal models. The aim of this study was to evaluate whether polymorphisms in this gene influence the development of type 2 diabetes (T2D) in humans.

Design: We investigated how genetic variations in the RPTP gene influence susceptibility to impaired glucose tolerance (IGT) and T2D, in Swedish men and women.

Methods: Genotyping of single nucleotide polymorphisms (SNPs) was performed by dynamic allele-specific hybridization in a total of 1057 Swedish Caucasians including 497 subjects with normal glucose tolerance (NGT), 262 subjects with IGT, and 298 patients with T2D.

Results: SNPs rs1143699, rs4807015, and rs1978237 were found to be associated with T2D. SNP rs1143699 was associated with male T2D patients when compared with NGT controls (odds ratio; OR = 1.57; P = 0.029). SNP rs4807015 showed association with T2D patients when compared with NGT controls (OR = 1.32; P = 0.025). Finally, SNP rs1978237 was associated with T2D patients when compared with NGT controls (OR = 1.59; P = 0.002). Logistic regression analysis demonstrated that for SNP rs1143699 in men, C/C homozygosity conveys an increased risk of T2D (OR = 2.19; P = 0.035), while SNP rs4807015 was associated with an increased risk of T2D in both men and women (OR = 1.74; P = 0.029). SNP rs1978237 also demonstrated a risk of T2D in men and women (OR = 1.59; P = 0.026).

Conclusions: This study provides evidence for association of SNPs in the RPTP gene with T2D in Swedish Caucasians. SNPs rs1143699, rs4807015, and rs1978237 confer an increased risk of developing T2D.