Association of nucleotide variations in the apolipoprotein B48 receptor gene (APOB48R) with hypercholesterolemia.
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.
Fujita
Yuko
Y
Department of Internal Medicine II, Nippon Medical School, Tokyo, Japan.
Ezura
Yoichi
Y
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.
Bujo
Hideaki
H
Departments of Genome Research and Clinical Application, and, of Clinical Cell Biology, Chiba University Graduate School, Chiba, Japan.
Nakajima
Toshiaki
T
Department of Molecular Biology-Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.
Takahashi
Kaneo
K
Awa Medical Association Hospital, Chiba, Japan.
Kamimura
Kouhei
K
Awa Medical Association Hospital, Chiba, Japan.
Iino
Yasuhiko
Y
Department of Internal Medicine II, Nippon Medical School, Tokyo, Japan.
Katayama
Yasuo
Y
Department of Internal Medicine II, Nippon Medical School, Tokyo, Japan.
Saito
Yasushi
Y
Departments of Genome Research and Clinical Application, and, of Clinical Cell Biology, Chiba University Graduate School, Chiba, Japan.
Emi
Mitsuru
M
Department of Molecular Biology-Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.
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*
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D018110:Receptors, Lipoprotein; C411291:apo B48 receptor; D002784:Cholesterol