title: Association of nucleotide variations in the apolipoprotein B48 receptor gene (APOB48R) with hypercholesterolemia.
abstract: Factors predisposing to the phenotypic features of high total cholesterol (T-Cho) in human plasma have not been clearly defined. Here we report an association between two variations in the apolipoprotein B48 receptor gene (APOB48R) and plasma T-Cho levels among 352 adult individuals in Japan. By analyzing phenotypic associations between age- and gender-adjusted levels of plasma T-Cho, low-density lipoprotein (LDL) cholesterol (LDL-C), and high-density lipoprotein (HDL) cholesterol (HDL-C), we detected a significant correlation between genotypes of the A419P variation and adjusted T-Cho levels. Among homozygous G-allele carriers (n=265), heterozygous carriers (n=78), and homozygous minor C-allele carriers (n=9), T-Cho levels were 2.43+/-0.21 mg/cm(3), 2.48+/-0.24 mg/cm(3), and 2.63+/-0.21 mg/cm(3), respectively, indicating a codominant T-Cho-elevating effect of the minor C-allele (r=0.15, P=0.007). A similar effect was detected for c.934-960/del (r=0.13, P=0.015). Linkage disequilibrium (LD) analysis detected significant LD among eight variant sites that included neighboring loci. Our results indicate that variations in APOB48R and nearby genes are among the many factors involved in hypercholesterolemia. The etiological studies should now include consideration of this novel aspect of the mechanism(s) leading to hypercholesterolemic disease.
authors.affiliation: Department of Internal Medicine II, Nippon Medical School, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Molecular Biology-Institute of Gerontology, Nippon Medical School, Kawasaki, Japan. ezura.mph@mri.tmd.ac.jp.|Department of Molecular Pharmacology, Institute of Medical Research, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan. ezura.mph@mri.tmd.ac.jp.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ezura
authors.affiliation: Departments of Genome Research and Clinical Application, and, of Clinical Cell Biology, Chiba University Graduate School, Chiba, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Bujo
authors.affiliation: Department of Molecular Biology-Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Awa Medical Association Hospital, Chiba, Japan.
authors.forename: Kaneo
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Awa Medical Association Hospital, Chiba, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Kamimura
authors.affiliation: Department of Internal Medicine II, Nippon Medical School, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iino
authors.affiliation: Department of Internal Medicine II, Nippon Medical School, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Katayama
authors.affiliation: Departments of Genome Research and Clinical Application, and, of Clinical Cell Biology, Chiba University Graduate School, Chiba, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Molecular Biology-Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Emi
mesh_terms: D000368:Aged; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004252:DNA Mutational Analysis; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018110:Receptors, Lipoprotein / Q000235:genetics*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D018110:Receptors, Lipoprotein; C411291:apo B48 receptor; D002784:Cholesterol