title: Hypercholesterolemia associated with splice-junction variation of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) gene.
abstract: Factors predisposing to the phenotypic features of higher total cholesterol (T-Cho) have not been clearly defined. Here we report an association between a C/T single nucleotide polymorphism at IVS17+8 in the inter-alpha-trypsin inhibitor heavy chain 4 gene (ITIH4) and plasma total cholesterol levels in 351 adult individuals from an east-central area of Japan. Age and gender-adjusted levels of plasma T-Cho, LDL-cholesterol, triglyceride, and HDL-cholesterol were analyzed. When we separate the subjects into two genotypic groups regarding this single nucleotide polymorphism (SNP), those who lack the T-allele had significantly higher plasma T-Cho levels than the others who bear T-allele (mean 252.3 mg/dl versus 241.7 mg/dl; p=0.009). Of the 309 individuals without the T-allele, approximately 90% presented with hypercholesterolemia, whereas only 10% were hypercholesterolemic among 42 individuals with the T-allele (p <0.0001). These data suggest that genetic variation at ITIH4 locus is one of the likely candidate determinants for plasma cholesterol metabolisms.
authors.affiliation: Department of Molecular Biology-Institute of Gerontology and Department of Internal Medicine II, Nippon Medical School, Kawasaki, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Molecular Biology-Institute of Gerontology and Department of Internal Medicine II, Nippon Medical School, Kawasaki, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ezura
authors.affiliation: Department of Molecular Biology-Institute of Gerontology and Department of Internal Medicine II, Nippon Medical School, Kawasaki, Japan. memi@nms.ac.jp.|Department of Molecular Biology-Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-8533, Japan. memi@nms.ac.jp.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Emi
authors.affiliation: Department of Molecular Biology-Institute of Gerontology and Department of Internal Medicine II, Nippon Medical School, Kawasaki, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Molecular Biology-Institute of Gerontology and Department of Internal Medicine II, Nippon Medical School, Kawasaki, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takada
authors.affiliation: Department of Molecular Biology-Institute of Gerontology and Department of Internal Medicine II, Nippon Medical School, Kawasaki, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iino
authors.affiliation: Department of Molecular Biology-Institute of Gerontology and Department of Internal Medicine II, Nippon Medical School, Kawasaki, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Katayama
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 Genome Research and Clinical Application and Department of Clinical Cell Biology, Chiba University Graduate School, Chiba, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Bujo
authors.affiliation: Department of Genome Research and Clinical Application and Department of Clinical Cell Biology, Chiba University Graduate School, Chiba, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000368:Aged; D000510:Alpha-Globulins / Q000235:genetics*; D000704:Analysis of Variance; D002784:Cholesterol / Q000097:blood; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015842:Serine Proteinase Inhibitors / Q000235:genetics*
chemical_list: D000510:Alpha-Globulins; D015842:Serine Proteinase Inhibitors; C011877:inter-alpha-inhibitor; D002784:Cholesterol