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Genetic association of low-density lipoprotein receptor-related protein 2 (LRP2) with plasma lipid levels
Authors:Mii Akiko  Nakajima Toshiaki  Fujita Yuko  Iino Yasuhiko  Kamimura Kouhei  Bujo Hideaki  Saito Yasushi  Emi Mitsuru  Katayama Yasuo
Affiliation:Department of Internal Medicine, Divisions of Neurology, Nephrology, and Rheumatology, Nippon Medical School, Tokyo, Japan. s3072@nms.ac.jp
Abstract:
AIM: Not all genetic factors predisposing phenotypic features of dyslipidemia have been identified. We studied the association between the low density lipoprotein-related protein 2 gene (LRP2) and levels of plasma total cholesterol (T-Cho) and LDL-cholesterol (LDL-C) among 352 adults in Japan.METHODS: Subjects were obtained from among participants in a cohort study that was carried out with health-check screening in an area of east-central Japan. We selected 352 individuals whose LDL-C levels were higher than 140 mg/dL from the initially screened 22,228 people. We assessed the relation between plasma cholesterol levels and single-nucleotide polymorphisms (SNPs) in the LRP2 gene.RESULTS: We identified significant correlations between plasma cholesterol levels and two of 19 examined SNPs in LRP2, c.+193826T/C and IVS55 - 147A/G. In particular, the association of c.+193826T/C with the T-Cho level was prominent (p=0.003), showing a co-dominant effect of the minor C-allele on lowering T-Cho and LDL-C levels: for 24 homozygous C-allele carriers, T-Cho=240.7 +/- 24.2 mg/dL and LDL-C=166.1 +/- 21.0 mg/dL); for 130 heterozygous carriers, 248.5 +/- 23.5 mg/dL and 166.6 +/- 19.3 mg/dL; and for 196 homozygous T-allele carriers, 253.9 +/- 23.5 mg/dL and 172.0 +/- 21.0 mg/dL. Linkage disequilibrium (LD) analyses based on 19 selected SNPs showed that c.+193826T/C and IVS55 - 147A/G were in tight LD and that both were located in an LD block covering the genomic sequence from exon 55 to exon 61.CONCLUSION: We confirm the association between LRP2 and levels of T-Cho and LDL-C in human plasma. The results suggest that genetic variations in LRP2 are important factors affecting lipoprotein phenotypes of patients with hypercholesterolemia.
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