Tetsuo Hayakawa

Variation of the Fatty Acid Binding Protein 2 Gene Is Not Associated With Obesity and Insulin Resistance in Japanese Subjects

An alanine to threonine substitution at codon 54 of the fatty acid binding protein 2 (FABP2) gene has been associated with insulin resistance in Pima Indians and with obesity in aboriginal Canadians. We investigated whether this polymorphism contributes to obesity and insulin resistance in 258 Japanese subjects. Thirty-six subjects (13.9%) were homozygous for the Thr54 allele, 106 (41.1%) were heterozygous for the Ala54/Thr54 allele, and 116 (45.0%) were homozygous for the Ala54 allele. The frequency of the Thr54 allele was 0.34 and did not differ significantly between men and women. The incidence of non-insulin-dependent diabetes mellitus (NIDDM) was not different among the three genotypes. The variation at codon 54 of the FABP2 gene was not associated with obesity, hypertension, dyslipidemia, hyperuricemia, or hyperinsulinemia. These results suggest that the polymorphism at codon 54 of the FABP2 gene is not a major contributing factor to obesity and insulin resistance in Japanese subjects.

Phenotypic characterization of the β3-adrenergic receptor mutation and the uncoupling protein 1 polymorphism in Japanese men

The Trp64Arg mutation of the beta3-adrenergic receptor (beta3AR) gene and A to G polymorphism of the uncoupling protein 1 (UCP1) gene are reported to be associated with weight gain, and both have been shown to have an additive effect on weight gain in Caucasians. Racial differences have also been noted in the beta3AR mutation; however, the effect of UCP1 polymorphism on body weight is not obvious in the Japanese. Thus, we investigated the association of genetic variations in beta3AR and UCP1 genes and the additive effects of these two genes in 214 Japanese men. The frequency of the Trp64Arg allele was 0.19, and serum triglyceride was significantly higher in Arg64 homozygotes versus Trp64 homozygotes. The frequency of the G allele was 0.51, and the body mass index (BMI) was significantly higher in subjects with the G allele (GG homozygotes and AG heterozygotes) versus those without it (AA homozygotes). The beta3AR mutation and UCP1 polymorphism were not found to have additive effects, and they were not related to glucose tolerance patterns and insulin resistance. Our results suggest that the beta3AR mutation is associated with hypertriglyceridemia and the UCP1 polymorphism may be a weak contributing factor to obesity in Japanese men.

Prediction of exercise-mediated changes in metabolic markers by gene polymorphism

The effects of regular physical exercise on obesity-associated metabolic abnormalities vary for each individual. In this study, we investigated whether genotypes of genes associated with obesity can predict the effects of exercise on changes in metabolic markers in healthy men. Healthy Japanese men (n=106) performed the exercise program at 50% of their maximal heart rate for 20-60 min a day, 2-3 days each week for 3 months. The levels of fasting plasma glucose (FPG) and serum leptin significantly decreased after the exercise program. Polymorphisms of the beta3-adrenergic receptor (beta3AR) and uncoupling protein-1 (UCP-1) genes were analyzed with RFLP methods. In the Trp/Trp genotype of the beta3AR gene, the levels of serum leptin, FPG and fructosamine (FrAm) decreased significantly after the exercise program, but not in the Arg/Arg genotype. In the AG heterozygote and the GG homozygote of the UCP-1 gene, FPG and FrAm levels were significantly reduced, respectively. In conclusion, gene polymorphism of the beta3AR and UCP-1 was found to be associated with the exercise-mediated improvement in glucose tolerance and leptin resistance in healthy Japanese men.

Renoprotective effects of atorvastatin compared with pravastatin on progression of early diabetic nephropathy

Several studies have shown that statins suppress the progression of diabetic nephropathy. However, few reports have directly compared the renoprotective effects between potent and conventional statins.

S20G mutation of the amylin gene in Japanese patients with type 2 diabetes.

Amylin is a major protein component of islet amyloid, and thought to be a pancreatic islet hormone that plays a role similar to insulin and glucagon in the maintenance of glucose homeostasis [1]. Recently, Sakagashira et al. [2] reported that a serine to glycine missense mutation at position 20 of the amylin molecule (S20G) was found in 4.1% of Japanese patients with type 2 diabetes and 10% of those with early-onset type 2 diabetes, whereas the mutation was not found in non-diabetic subjects and type 1 diabetic patients. Racial differences have been noted in the frequency and role of the S20G mutation in association with the development of diabetes. No mutation was found in Caucasians [3–5]. The mutation was found in Chinese and Taiwanese subjects, but an association with diabetes was only established among the former [6,7]. In contrast to the findings of Sakagashira et al., Yamada et al. [8] reported that the frequency of the mutation was not statistically different between Japanese type 2 diabetic patients and subjects with normal glucose tolerance (NGT). To help clarify this apparent inconsistency in the role of the S20G mutation in the development of diabetes in Japanese subjects, we investigated the mutation in 308 Japanese patients with type 2 diabetes aged from 20 to 89 years (60.9912.2 years, mean9SD), and 149 NGT subjects with no family histories of diabetes aged from 40 to 67 years (50.996.3 years, mean9SD). Type 2 diabetes and NGT were defined by the World Health Organization (WHO) criteria. In the type 2 diabetic patients (a total of 175 men and 133 women), 150 subjects had family histories of dia* Corresponding author. Tel.: +81-76-2652234; fax: +8176-2344250.

Idiopathic adulthood ductopenia

In 1981, a 26 year old man occasionally demonstrated elevated serum transaminase concentrations. He had no history of medication, or a personal or family history of jaundice, except for prolonged physiological jaundice as a neonate. Serum hepatitis B surface antigen, hepatitis C virus antibody and anti‐mitochondrial antibody were absent. A wedge biopsy specimen revealed ductular proliferation, mild inflammation of the portal area and disappearance of bile ducts from 80% of the portal tracts. Serial sections demonstrated a vanishing bile duct. Endoscopic retrograde choledo‐chopancreatography, portography and arteriography demonstrated no abnormalities. In 1994, the patient died of hepatic failure following a 12 year observation period. He was subsequently diagnosed with idiopathic adulthood ductopenia on the basis of the criteria proposed by Ludwig.