GH secretagogue receptor gene polymorphisms are associated with stature throughout childhood

Abstract

Context: Ghrelin plays a major role in GH physiology and energy metabolism. Polymorphisms of its receptor (GH secretagogue receptor (GHSR)) may influence childhood growth and weight regulation. Objective: To correlate GHSR polymorphisms with auxological parameters throughout childhood in a healthy cohort. Study design: Longitudinal retrospective population-based genetic association study. Subjects and methods: GHSR genotypes were evaluated in 1362 children and compared with height/length, weight, and body mass index (BMI) data across an observation span of 10 years (0, 1, 3, 5, 8, and 10 years). Five different GHSR SNPs (rs2922126, rs2981464, rs482204, rs562416, and rs572169), minor allele frequency O0.1, were genotyped. Identification of potential genetic associations with height, weight, and BMI, using additive and dominant/recessive models, was optimized by comparing allele or genotype frequencies between the tallest and the shortest 27% of subjects for each auxological variable. Significance of association was evaluated by c 2 test. Results: The rs482204 TT genotype, vs TC/CC, was associated with greater stature across the entire observation period (P!0.05). Similarly, the rs562416 TT genotype, vs TG/GG, correlated positively with tall stature at 3, 8, and 10 years. Other SNPs and genotypes showed no association with height at any age. No association was found between any tested SNPs and weight or BMI. Conclusions: Longitudinal investigation between birth and 10 years in a population-based cohort revealed a significant association of the rs482204 and rs562416 GHSR polymorphisms on height, whereas no association between GHSR polymorphisms and weight or BMI was ascertainable.

Enhanced responsiveness of Ghsr Q343X rats to ghrelin results in enhanced adiposity without increased appetite

“…On the other hand, our observations are consistent with those in Ghsr -/-mice supporting that ghrelin-GHSR signal is not a key contributor to somatic growth in rodents (10). In contrast, several genetic studies support the role of GHSR as a physiological contributor in humans both to the adult height variance among individuals (23)(24)(25) and to the nosology of somatic growth disorders (22,45,46).…”

“…GHSR promotes somatic growth in humans, presumably through growth hormone secretagogue properties, but its association with obesity risk is inconsistent (22)(23)(24)(25)(26) although dysregulated amounts of the orexigenic acyl ghrelin correlate with obesity features associated with a common single-nucleotide polymorphism at the FTO locus (27).…”

“…The hormone ghrelin and its receptor induce potent biological responses such as food intake, adipogenesis, and growth hormone secretion, but the physiological roles of both the hormone and receptor still remain incompletely defined by currently available genetic studies (21). GHSR promotes somatic growth in humans, presumably through growth hormone secretagogue properties, but its association with obesity risk is inconsistent (22)(23)(24)(25)(26), although dysregulated amounts of the orexigenic acyl ghrelin correlate with obesity features associated with a common single-nucleotide polymorphism at the FTO locus (27). Although Ghsr −/− mice consistently demonstrate a decreased motivation for hedonic eating (28,29), these animals do not clearly show altered body weight or energy intake (10,(30)(31)(32), suggesting that GHSR is not a key regulator of food intake or body weight or, alternatively, that GHSR knockdown induces a compensatory response to maintain normal phagic drive and body weight.…”

A study of genetic markers of human height

“…Также показано, что мутации в данном гене ассоцииро-ваны с низкорослостью (Riedl et al, 2012). Белковый продукт гена HHIP является сигнальной молекулой, которая играет важную роль в регуляции морфогене-за.…”