The Impact of PNPLA3 rs738409 Genetic Polymorphism and Weight Gain ≥10 kg after Age 20 on Non-Alcoholic Fatty Liver Disease in Non-Obese Japanese Individuals.
Non-alcoholic fatty liver disease (NAFLD) in non-obese individuals is inadequately elucidated. We aim to investigate the impact of known genetic polymorphisms on NAFLD and the interaction between genetic risks and weight gain on NAFLD in obese and non-obese Japanese individuals. A total of 1164 participants who received health checkups were included. Participants with excessive alcohol consumption, with viral hepatitis or other inappropriate cases were excluded. Fatty liver was diagnosed by ultrasonography. Participants with a body mass index (BMI) of <18.5 kg/m2, 18.5-22.9 kg/m2, 23.0-24.9 kg/m2 and ≥25 kg/m2 were classified underweight, normal weight, overweight and obese, respectively. Self-administered questionnaire for lifestyle was assessed and a total of 8 previously reported genetic polymorphisms were chosen and examined. In all, 824 subjects were enrolled. The overall prevalence of NAFLD was 33.0%: 0% in underweight, 15.3% in normal weight, 41.1% in overweight and 71.7% in obese individuals. The prevalence of NAFLD is more affected by the G allele of patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 in normal weight (odds ratio (OR) 3.52; 95%-CI: 1.42-8.71; P = 0.0063) and in overweight individuals (OR 2.60; 95%-CI: 1.14-5.91; P = 0.0225) than in obese individuals (not significant). Moreover, the G allele of PNPLA3 rs738409 and weight gain ≥10 kg after age 20 had a joint effect on the risk of NAFLD in the normal weight (OR 12.00; 95% CI: 3.71-38.79; P = 3.3×10-5) and the overweight individuals (OR 13.40; 95% CI: 2.92-61.36; P = 0.0008). The G allele of PNPLA3 rs738409 is a prominent risk factor for NAFLD and the interaction between the PNPLA3 rs738409 and weight gain ≥10 kg after age 20 plays a crucial role in the pathogenesis of NAFLD, especially in non-obese Japanese individuals.
Health Care Division, Kyoto Second Red Cross Hospital, Kyoto, Kyoto, Japan.
Kenichi
K
Nishioji
Health Care Division, Kyoto Second Red Cross Hospital, Kyoto, Kyoto, Japan.
Naomi
N
Mochizuki
Health Care Division, Kyoto Second Red Cross Hospital, Kyoto, Kyoto, Japan.
Masao
M
Kobayashi
Health Care Division, Kyoto Second Red Cross Hospital, Kyoto, Kyoto, Japan.
Mai
M
Kamaguchi
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
Yoshio
Y
Sumida
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
Takeshi
T
Nishimura
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
Kanji
K
Yamaguchi
Department of Psychiatry, Shiga University of Medical Science, Otsu, Shiga, Japan.
Hiroshi
H
Kadotani
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
Yoshito
Y
Itoh
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001219:Aspartate Aminotransferases / Q000097:blood; D015992:Body Mass Index; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007564:Japan; D008049:Lipase; D008055:Lipids / Q000097:blood; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D009765:Obesity / Q000208:ethnology / Q000235:genetics; D016017:Odds Ratio; D050177:Overweight / Q000208:ethnology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D015430:Weight Gain / Q000208:ethnology / Q000235:genetics*; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D008049:Lipase; D008055:Lipids; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent