title: Identification of novel human GH-1 gene polymorphisms that are associated with growth hormone secretion and height.
abstract: Height, which is partially determined by GH secretion, is genetically influenced. The purpose of this study was to identify polymorphisms in the GH-1 gene, which are associated with altered GH production. The subjects included prepubertal short children with GH insufficiency without gross pituitary abnormalities (n = 43), short children with normal GH secretion (n = 46), and normal adults (n = 294). A polymorphism in intron 4 (P-1, A or T at base 1663) was identified. Two additional polymorphic sites (P-2, T or G at base 218, and P-3, G or T at base 439) in the promoter region of the GH-1 gene were also identified and matched with the P-1 polymorphism (A or T, respectively) in more than 90% of the subjects. P-1, P-2, and P-3 were considered to be associated with GH production, and the results of P-2 are explained as a representative in this abstract. For example, the allele frequency of T at P-2 in prepubertal short children with GH insufficiency without gross pituitary abnormalities (58.1%) was significantly different from that in short children with normal GH secretion and normal adults (37.0% and 43.5%, respectively; P < 0.001). Furthermore, significant differences were observed in maximal GH peaks in provocative tests (11.1 vs. 18.2 ng/mL, P = 0.006), insulin-like growth factor I SD scores (SDS) (-2.4 vs. -0.8, P < 0.0001), and height (Ht) SDS (-3.7 vs. -3.0, P = 0/001) in children with the T/T or G/G genotypes at P-2, respectively. In the entire study group, significant differences in insulin-like growth factor SDS (T/T, -0.9; G/G, -0.2; P = 0.0009) and Ht SDS (T/T, -1.0; G/G, -0.4; P = 0.022) were observed between the T/T and G/G genotypes at P-2. These data indicate that GH secretion is partially determined by polymorphisms in the GH-1 gene, which explain some of the variations in GH secretion and Ht.
authors.affiliation: Endocrinology, Metabolism and Genetics Unit, Tokyo Metropolitan Kiyose Children's Hospital, Japan. eet.yhaseg@chp.kiyose.tokyo.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: K
authors.initials: K
authors.lastname: Fujii
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Igarashi
authors.forename: K
authors.initials: K
authors.lastname: Tachibana
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Onigata
authors.forename: Y
authors.initials: Y
authors.lastname: Nishi
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D000328:Adult; D000483:Alleles; D001827:Body Height / Q000235:genetics* / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005796:Genes / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D019382:Human Growth Hormone / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology*; D012150:Polymorphism, Restriction Fragment Length; D018401:Sample Size
chemical_list: D019382:Human Growth Hormone; D004247:DNA