Role of Ghrelin Polymorphisms in Obesity Based on Three Different Studies

Abstract

Res. 2002;10: 782-791. Objective: Associations between preproghrelin DNA variants and obesity-related phenotypes were studied in 3004 subjects from the Québec Family Study (QFS), the HERI-TAGE Family Study (HERITAGE), and the Swedish Obese Subjects (SOS) Study. Research Methods and Procedures: Body mass index (BMI), fat mass (FM) from underwater weighing, and abdominal fat from computerized tomography were measured. The ghrelin polymorphisms were identified by polymerase chain reaction. Results: Arg51Gln QFS subjects (n ϭ 6) had lower ghrelin concentrations (p ϭ 0.007) than Arg51Arg subjects (n ϭ 14). White preproghrelin Met72Met subjects in HERI-TAGE had the lowest BMI (p ϭ 0.020), and those in the QFS cohort had the lowest FM (p Ͻ 0.001). Met72 carrier status (Met72ϩ) was associated with lower FM (p ϭ 0.026) and higher insulin-like growth factor-1 levels (p ϭ 0.019) among blacks. Met72Met QFS subjects had less visceral fat (p ϭ 0.002) and a lower fasting respiratory quotient (p ϭ 0.037). HERITAGE Met72ϩ white subjects also showed lower exercise respiratory quotient (p ϭ 0.030) and higher maximal oxygen uptake (p ϭ 0.023). Furthermore, the prevalence of Met72ϩ was higher (19.2%; p Ͻ 0.05) in SOS subjects whose BMI was Յ25 kg/m 2 than in those with BMI Ͼ25 kg/m 2 (14.8%). SOS Met72ϩ obese women had a lower (11.4%; p ϭ 0.032) prevalence of hypertension than noncarriers (23.9%). Discussion: Arg51Gln mutation was associated with lower plasma ghrelin levels but not with obesity. The preproghrelin Met72 carrier status seems to be protective against fat accumulation and associated metabolic comorbidities.

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

“…It has been demonstrated that Preproghrelin Leu72Met variant and obesity M Kuzuya et al the frequency of the 72Met allele of the preproghrelin gene is approximately 8% in the Caucasian population and approximately 2% in the black population in three different cohorts. 10 Compared with these previous studies, the frequency of the 72Met allele in our Japanese cohort was much higher than that observed in Caucasian or African populations, probably reflecting genetic/ethnic heterogeneity. The Leu72Met polymorphism of preproghrelin was previously found in a group of obese French children and adolescents.…”

“…It has been reported that Leu72Met polymorphism is associated with triglyceride or lipoprotein (a) levels. 10,17 In the present study, however, we observed no association between serum lipid levels, fasting glucose, insulin, HbA1c or HOMA-IR levels and preproghrelin Leu72Met genotypes.…”

“…7 One of these nucleotide changes, a single-base substitution C214A with Met replacing Leu at codon 72 in the preproghrelin amino-acid sequence, seems to be associated with an earlier onset of obesity, [7][8][9] but it has also been proposed that 72Met could provide protection against the accumulation of fat. 10 Thus, previous studies on preproghrelin genetic variants have arrived at contradictory findings as to their role in obesity. Additionally, most studies have had only child and adolescent subjects, whereas few studies have targeted the middle aged or elderly, or randomly sampled communitydwelling individuals.…”

Ghrelin in obesity and endocrine diseases

“…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). Furthermore, one study of 3004 subjects even reported the Leu72Met polymorphism to be protective against fat accumulation; the polymorphism was related to lower BMI, fat mass and reduced visceral fat (Ukkola et al, 2002). Another study suggests that Leu72 allele carriers are more prone to weight variability in response to environmental factors given the reduced frequency of Leu72Met polymorphism in monozygotic twins discordant for obesity (Leskela et al, 2009).…”

“…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.…”