Lack of association of LRP5 and LRP6 polymorphisms with type 2 diabetes mellitus in the Japanese population.
OBJECTIVE
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-beta, 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.
Zenibayashi
Masako
M
Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.
Miyake
Kazuaki
K
Horikawa
Yukio
Y
Hirota
Yushi
Y
Teranishi
Tetsuya
T
Kouyama
Kunichi
K
Sakaguchi
Kazuhiko
K
Takeda
Jun
J
Kasuga
Masato
M
D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; C555475:LRP6 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555483:Lrp5 protein, mouse; C555476:Lrp6 protein, mouse