Preproghrelin Leu72Met variant contributes to overweight in middle-aged men of a Japanese large cohort

Abstract

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 (BMIX25 kg/m 2 ) of middle-aged men than in the normalweight 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.

Genetic Association between Ghrelin Polymorphisms and Alzheimer’s Disease in a Japanese Population

“…Interestingly, rs696217 (Leu72Met) has been reported to affect susceptibility to bulimia nervosa in a Japanese population [12]. Moreover, the polymorphism has also been found to be associated with obesity, blood pressure, impaired glucose tolerance and risk for type II diabetes mellitus [13,14,15,16]. Although these metabolic factors might modulate risk for AD, our data did not show any association between rs696217 and AD.…”

Ghrelin in obesity and endocrine diseases

“…We studied the ghrelin gene in obese French children and found a positive correlation between the Leu72Met heterozygote variant with higher BMI and early-onset obesity and a similar significant association between the Leu72Met polymorphism and earlyonset obesity was observed in Italian children (Miraglia Del et al, 2004). In addition, the Leu72Met polymorphism has been suggested to contribute to weight gain in middle-aged Japanese men (Kuzuya et al, 2006). However, the above findings could not be reproduced by other studies (Bing et al, 2005;Hinney et al, 2002;Jo et al, 2005;Zhu et al, 2010).…”

“…Relationships have been described between obesity and genomic variants of the ghrelin (GHRL) (Gueorguiev et al, 2009;Korbonits et al, 2002;Kuzuya et al, 2006;Leskela et al, 2009;Miraglia Del et al, 2004;Ukkola et al, 2001;Ukkola et al, 2002) M a n u s c r i p t 12 and ghrelin receptor (GHS-R) (Baessler et al, 2005;Gueorguiev et al, 2009;Liu et al, 2007) genes.…”

Р. Leu72met Mutation of Ghrelin GHRL Gene in Children With Gastroesophageal Reflux Disease

“…It must be noted, that the study of such genetic locus among Ukrainians was not carried out, and we first inform about the frequencies of alleles of р. [30,31]. The frequency of Met72 allele in our sample is 21 %, a bit higher than the data, given by НарМар (15,6 %, N = 90).…”