Sources of variation of transthyretin in healthy subjects in East and Southeast Asia: Clinical and experimental evidence for the effect of alcohol on transthyretin metabolism.
BACKGROUND
Although transthyretin (TTR), a negative acute phase protein, is recognized as one of the nutrition assessment proteins, factors affecting serum TTR concentrations than nutritional state in healthy subjects have not been well understood. We investigated the sources of variation of serum TTR concentrations in healthy subjects.


METHODS
Serum samples of 3511 healthy volunteers (2055 of Japanese subjects and 1456 of other East and Southeast Asian subjects) were collected. We measured serum TTR concentrations in addition to routine blood examinations in each sample, and assessed the relationship between each serum TTR concentrations and the clinical indices such as age, sex, body mass index (BMI), smoking, and level of daily alcohol consumption. We also investigated the direct alcohol effect of TTR expression by assessing TTR mRNA and protein levels in vivo and in vitro experiments.


RESULTS
Mean TTR concentrations of males were prominently higher than those of females. Multiple regression analysis revealed that serum TTR concentrations increased with age, BMI, and the level of daily alcohol consumption after adjustment for a slight regional difference. Moreover, TTR expression was up-regulated by alcohol treatment through hepatocyte nuclear factor 4α (HNF-4α) in vitro and in vivo experiments.


CONCLUSIONS
Sex, aging, BMI, and the level of daily alcohol consumption may be the factors affecting serum TTR concentrations in healthy subjects.
Department of Pharmacy, Kumamoto University Hospital, Kumamoto, Japan; Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: hjono@fc.kuh.kumamoto-u.ac.jp.
Hirofumi
H
Jono
Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Yu
Y
Su
Diagnostic Unit for Amyloidosis, Kumamoto University Hospital, Kumamoto, Japan; Department of Laboratory Medicine, Kumamoto University Hospital, Kumamoto, Japan.
Konen
K
Obayashi
Department of Laboratory Medicine, Kumamoto University Hospital, Kumamoto, Japan.
Yoko
Y
Tanaka
Department of Clinical Laboratory, Yamaguchi University Hospital, Yamaguchi, Japan.
Akiyo
A
Ishiguro
Department of Laboratory Medicine, Kumamoto University Hospital, Kumamoto, Japan.
Hitoshi
H
Nishimura
Diagnostic Unit for Amyloidosis, Kumamoto University Hospital, Kumamoto, Japan; Department of Laboratory Medicine, Kumamoto University Hospital, Kumamoto, Japan.
Satoru
S
Shinriki
Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Mitsuharu
M
Ueda
Department of Laboratory Medicine, Kumamoto University Hospital, Kumamoto, Japan.
Katsuyoshi
K
Ikeda
Department of Medical Biochemistry, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Kazuya
K
Yamagata
Faculty of Health Science, Department of Clinical Laboratory Sciences, Yamaguchi University, Japan.
Kiyoshi
K
Ichihara
Department of Laboratory Medicine, Kumamoto University Hospital, Kumamoto, Japan; Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Yukio
Y
Ando
D000328:Adult; D000367:Age Factors; D000438:Alcohols / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D001210:Asia, Southeastern; D005202:Asia, Eastern; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D064368:Healthy Volunteers; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D015999:Multivariate Analysis; D011228:Prealbumin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D012016:Reference Values; D014407:Tumor Cells, Cultured; D055815:Young Adult
D000438:Alcohols; D011228:Prealbumin
Age; Alcohol; BMI; Regional difference; Transthyretin