Aims. A missense mutation in the low density lipoprotein receptor-related protein 6 gene (
LRP6) was recently shown to be responsible for a disorder characterized by early-onset coronary artery disease as well as diabetes mellitus (DM), hyperlipidemia, hypertension, and osteoporosis. Mice deficient in LRP5, a closely related paralog of LRP6, manifest a marked impairment in glucose tolerance. The aim of the present study was to examine whether common variants of
LRP5 and
LRP6 are associated with Type 2 DM or dyslipidemia in Japanese individuals.
Methods. Thirteen single nucleotide polymorphisms (SNPs) of
LRP6 and nine SNPs of
LRP5 were genotyped in a total of 608 Type 2 DM patients and 366 nondiabetic control subjects (initial study). An association analysis was then performed for each SNP and for haplotypes. For some of the SNPs, we provided another sample panel of 576 cases and 576 controls for the replication study. The relation to clinical characteristics was also examined in diabetic subjects.
Results. In the initial study, three SNPs of
LRP6 were found to be associated with susceptibility to Type 2 DM. However, this association was not detected in the replication panel. None of SNPs in
LRP5 were associated with Type 2 DM in the initial panel. Neither
LRP6 nor
LRP5 was associated with body mass index, HOMA-β, HOMA-IR or serum lipid concentrations.
Conclusions. We found no evidence for a substantial effect of
LRP5 or
LRP6 SNPs on susceptibility to type 2 diabetes or clinical characteristics of diabetic subjects in Japanese population.
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