Variations in the preproghrelin gene correlate with higher body mass index, fat mass, and body dissatisfaction in young Japanese women

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Abstract
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.