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Background: Angiopoietin-like protein 8 (ANGPTL8) is considered to be metabolically multifunctional. One notable function still to be elucidated definitively is a betatrophic role in protecting and preserving pancreatic beta-cell function. There is, however, a paucity of data regarding the role of ANGPTL8 in the etiology of type 2 diabetes (T2D), but some findings of human research have suggested the potential for significant involvement., Objective: To examine the frequency of T2D and impaired glucose tolerance (IGT) in Japanese subjects with the ANGPTL8 R59W variant., Methods: ANGPTL8 R59W (Rs2278426, c.194C > T) was determined by polymerase chain reaction-restriction fragment length polymorphism using the restriction enzyme FokI in 797 consecutive Japanese individuals. Subjects with triglyceride levels greater than or equal to 150 mg/dL were considered to be hypertriglyceridemic., Results: Genotype frequencies of ANGPTL8 R59W were as follows: wild-type RR (C/C) 53.5%, RW (C/T) 36.6%, and WW (T/T) 9.9%. T2D and IGT were significantly prevalent in WW and RW subjects relative to RR among all 797 subjects (P = .0138) and also in hypertriglyceridemic subjects (P = .0015). In multiple logistic regression models for the existence of T2D and IGT in hypertriglyceridemic subjects, the odds ratio for heterozygote RW and homozygote WW genotypes to wild-type RR was 2.406 (P = .0017) after controlling the risk factors of age, gender, and body mass index as covariates., Conclusions: The frequency of ANGPTL8 R59W is significantly higher in Japanese subjects than in other ethnic groups. The rates of T2D and IGT were greater in subjects with the R59W variant. These findings indicate that ANGPTL8 is a participant in diabetes and a potential therapeutic target for T2D prevention, especially in East Asians., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Adrenomedullin 2/intermedin (AM2/IMD) is a novel vasodilator peptide with various effects on the renal function and cardiovascular system. An exonic insertion (I)/deletion (D) polymorphism (rs3840963) may influence generation of AM2/IMD-53, due to its location within the N-terminal sequence. We investigated the association of this polymorphism with blood pressure, renal function and the risk of silent cerebrovascular lesions in a Japanese population recruited from the Ohasama study. We recorded 24 h ambulatory blood pressure (ABP), estimated glomerular filtration rate (eGFR) and proteinuria of 1073 individuals over 40 years of age. Silent cerebrovascular lesions (lacunar infarction and white matter hyperintensity (WMH)) were recorded in 794 individuals over 55 years of age. Chronic kidney disease (CKD) was diagnosed in individuals with proteinuria and/or decreased eGFR ≤60 ml min(-1) per 1.73 m(2). DD carriers, compared with II and ID carriers, displayed significantly higher 24 h ABP (127.4 vs. 122.0 and 122.9 mm Hg, respectively, in systolic ABP, P=0.009; and 74.8 vs. 71.3 and 72.5 mm Hg, respectively, in diastolic ABP, P=0.002), and lower eGFR (75.4 vs. 82.6 and 82.9 ml min(-1) per 1.73 m(2), respectively, P=0.04). DD carriers also had a significantly higher odds ratio (OR) for prevalence of CKD (OR: 2.7, P=0.003), presence of lacunar infarction (OR: 2.4, P=0.01) and WMH (OR: 2.7, P=0.003), compared with II carriers. The AM2/IMD I/D polymorphism is associated with renal dysfunction, blood pressure regulation and asymptomatic cerebrovascular diseases in the Japanese general population.

Background: Ghrelin is an endogenous peptide that stimulates growth hormone secretion, enhances appetite, and increases body weight and may play a role in eating disorders., Objective: The purpose was to determine whether any preproghrelin gene variants are associated with anthropometric measures, circulating ghrelin, lipid concentrations, insulin resistance, or psychological measures relevant to eating disorders in young women., Design: This cross-sectional study compared outcome measures between preproghrelin genotypes. The participants in the study included 264 Japanese women [university students with a mean (+/-SD) age of 20.4 +/- 0.7] with no history of eating disorders. The main outcomes were responses to the Eating Disorder Inventory-2 (EDI-2), anthropometric measures, measures of depression and anxiety, and fasting blood concentrations of acylated or desacyl ghrelin, lipids, glucose, and insulin., Results: Two single nucleotide polymorphisms (SNPs) whose minor allele frequencies were >0.05--the Leu72Met (408 C-->A) SNP in exon 2 and the 3056 T-->C SNP in intron 2--were used for association analysis. The 3056C allele was significantly associated with a higher acylated ghrelin concentration (P=0.0021), body weight (P=0.011), body mass index (P=0.007), fat mass (P=0.012), waist circumference (P=0.008), and skinfold thickness (P=0.011) and a lower HDL-cholesterol concentration (P=0.02). Interestingly, the 3056C allele was related to elevated scores in the Drive for Thinness-Body Dissatisfaction (DT-BD) subscale of the EDI-2 (P=0.003)., Conclusion: Our findings suggest that the preproghrelin gene 3056T-->C SNP is associated with changes in basal ghrelin concentrations and physical and psychological variables related to eating disorders and obesity.

Objective: To investigate whether Leu72Met polymorphism of the preproghrelin gene is associated with overweight/obesity in middle-aged and older Japanese., Design: Cross-sectional analysis., Subjects: A total of 2238 community-dwelling middle-aged and older Japanese people (age: 40-79 years) who participated in the first wave of examinations in the National Institute for Longevity Sciences - Longitudinal Study of Aging from April 1998 to March 2000., Measurements: The Leu72Met polymorphism of prepoghrelin gene, anthropometric variables including body weight, body mass index (BMI), waist circumference, waist-to-hip ratio and whole-fat mass and biochemical variables including serum lipid levels, fasting plasma glucose, insulin and homeostasis model assessment for insulin resistance., Results: The frequencies of the Leu72Leu, Leu72Met and Met72Met alleles were 63.4, 32.7 and 4.0%, respectively. No differences in the genotype distributions of the Leu72Met polymorphism were found between genders or age groups, and no significant associations were observed between polymorphism and anthropometric variables in women and older men. However, middle-aged men who were 72Met allele carriers showed a higher body weight change from body weight at 18 years of age, as well as a higher waist circumference and a tendency to a higher waist-hip-ratio than noncarriers. Although there were no significant differences in the genotype distribution according to BMI in women and older men, a significantly higher frequency of the 72Met allele was found in the higher BMI group (BMI> or =25 kg/m(2)) of middle-aged men than in the normal-weight group. No significant associations were observed between polymorphism and serum lipid, glucose or insulin levels., Conclusions: These results suggest that the 72Met allele of the preproghrelin gene is a contributing factor for midlife weight change in men.