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/cm3, 2.48±0.24 mg/cm3, and 2.63±0.21 mg/cm3, 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.
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Acknowledgements
We thank Mitsuko Kajita, Mina Kodaira, Miho Kawagoe, Tamami Uchida, and Naoko Tsuruta for their expert technical assistance. This work was supported by a grant for Strategic Research from the Ministry of Education, Science, Sports, and Culture of Japan; by a Research Grant for Research from the Ministry of Health and Welfare of Japan; and by a Research for the Future Program Grant of The Japan Society for the Promotion of Science.
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Fujita, Y., Ezura, Y., Bujo, H. et al. Association of nucleotide variations in the apolipoprotein B48 receptor gene (APOB48R) with hypercholesterolemia. J Hum Genet 50, 203–209 (2005). https://doi.org/10.1007/s10038-005-0240-1
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DOI: https://doi.org/10.1007/s10038-005-0240-1
