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.
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