Polymorphisms of Interleukin-1β and β3-Adrenergic Receptor in Japanese Patients With Nonalcoholic Steatohepatitis

Authors

  • Yasuko Nozaki,

    1. Department of Gastroenterology and Hepatology (YNo, TS, YNe, MO, NA, SI, SO) and Department of Pathology (YH, MH, HE), Kochi Medical School, Kochi, Japan.
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  • Toshiji Saibara,

    Corresponding author
    1. Department of Gastroenterology and Hepatology (YNo, TS, YNe, MO, NA, SI, SO) and Department of Pathology (YH, MH, HE), Kochi Medical School, Kochi, Japan.
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  • Yoshihisa Nemoto,

    1. Department of Gastroenterology and Hepatology (YNo, TS, YNe, MO, NA, SI, SO) and Department of Pathology (YH, MH, HE), Kochi Medical School, Kochi, Japan.
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  • Masafumi Ono,

    1. Department of Gastroenterology and Hepatology (YNo, TS, YNe, MO, NA, SI, SO) and Department of Pathology (YH, MH, HE), Kochi Medical School, Kochi, Japan.
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  • Naoaki Akisawa,

    1. Department of Gastroenterology and Hepatology (YNo, TS, YNe, MO, NA, SI, SO) and Department of Pathology (YH, MH, HE), Kochi Medical School, Kochi, Japan.
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  • Shinji Iwasaki,

    1. Department of Gastroenterology and Hepatology (YNo, TS, YNe, MO, NA, SI, SO) and Department of Pathology (YH, MH, HE), Kochi Medical School, Kochi, Japan.
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  • Yoshihiro Hayashi,

    1. Department of Gastroenterology and Hepatology (YNo, TS, YNe, MO, NA, SI, SO) and Department of Pathology (YH, MH, HE), Kochi Medical School, Kochi, Japan.
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  • Makoto Hiroi,

    1. Department of Gastroenterology and Hepatology (YNo, TS, YNe, MO, NA, SI, SO) and Department of Pathology (YH, MH, HE), Kochi Medical School, Kochi, Japan.
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  • Hideaki Enzan,

    1. Department of Gastroenterology and Hepatology (YNo, TS, YNe, MO, NA, SI, SO) and Department of Pathology (YH, MH, HE), Kochi Medical School, Kochi, Japan.
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  • Saburo Onishi

    1. Department of Gastroenterology and Hepatology (YNo, TS, YNe, MO, NA, SI, SO) and Department of Pathology (YH, MH, HE), Kochi Medical School, Kochi, Japan.
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Reprint requests: Toshiji Saibara, MD, Department of Gastroenterology and Hepatology, Kochi Medical School 783-8505 Japan; Fax: +81-88-880-2338; E-mail: saibarat@kochi-ms.ac.jp.

Abstract

Background: Obesity, hypertriglyceridemia, and diabetes have been reported as frequent complications observed in patients with nonalcoholic steatohepatitis (NASH) in Western countries. The aim of this study was to investigate the genetic predisposition on NASH pathogenesis in the Japanese population.

Methods: Genotypes of two previously described functional polymorphisms—β3-adrenergic receptor 190 T/A polymorphism, which results in Trp64Arg (W64R) amino acid replacement, and interleukin-1β-511 T/C polymorphism in the promoter sequence—were determined in 63 Japanese NASH patients and 100 healthy volunteers using polymerase chain reaction and restriction fragment length polymorphism.

Results: β3-adrenergic receptor R allele frequency and the R/− (W/R and R/R) genotype frequency were significantly higher in NASH patients than those in control subjects. Interleukin-1β-511 T allele frequency and the T/T genotype frequency were significantly higher in NASH patients than those in control subjects. Obesity, hypertriglyceridemia, and hyperinsulinemia were associated with NASH patients with the R/− genotype, whereas an increase in fasting plasma glucose level and a decrease in insulinogenic index were associated with NASH patients with the W/W genotype.

Conclusion: This study confirmed the contribution of obesity, glucose intolerance, and hypertriglyceridemia to NASH development in the Japanese population. In addition to these factors, genetic predispositions to obesity and inflammation in the Japanese population were shown to contribute much to the development of NASH.

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