Hypercholesterolemia associated with splice-junction variation of inter-α-trypsin inhibitor heavy chain 4 (ITIH4) gene

• Published in: Journal of human genetics Vol. 49; no. 1; pp. 24 - 28
• Main Authors: Fujita, Yuko, Ezura, Yoichi, Emi, Mitsuru, Sato, Keiko, Takada, Daisuke, Iino, Yasuhiko, Katayama, Yasuo, Takahashi, Kaneo, Kamimura, Kouhei, Bujo, Hideaki, Saito, Yasushi
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.01.2004
• Subjects: Aged; Alpha-Globulins - genetics; Analysis of Variance; Biomedicine; Cholesterol - blood; Chromosomes, Human, Pair 3 - genetics; Cohort Studies; Female; Gene Expression; Gene Function; Gene Therapy; Genetic Variation; Human Genetics; Humans; Hypercholesterolemia - blood; Hypercholesterolemia - genetics; Japan; Male; Middle Aged; Molecular Medicine; Original Article; Polymorphism, Single Nucleotide - genetics; Serine Proteinase Inhibitors - genetics; Japan; Modifier gene; Inter-alpha-trypsin inhibitor heavy chain 4; Plasma total cholesterol (T-Cho); Single nucleotide polymorphism (SNP)
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1007/s10038-003-0101-8

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.