Identification of novel human GH-1 gene polymorphisms that are associated with growth hormone secretion and height

Yukihiro Hasegawa, Katsura Fujii, Makoto Yamada, Yutaka Igarashi, Katsuhiko Tachibana, Toshiaki Tanaka, Kazumichi Onigata, Yoshikazu Nishi, Shigeaki Kato, Tomonobu Hasegawa

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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.

Original languageEnglish
Pages (from-to)1290-1295
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume85
Issue number3
DOIs
Publication statusPublished - 2000

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Forensic Anthropology
Polymorphism
Growth Hormone
Genes
Genotype
Somatomedins
Insulin-Like Growth Factor I
Genetic Promoter Regions
Introns
Gene Frequency

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Identification of novel human GH-1 gene polymorphisms that are associated with growth hormone secretion and height. / Hasegawa, Yukihiro; Fujii, Katsura; Yamada, Makoto; Igarashi, Yutaka; Tachibana, Katsuhiko; Tanaka, Toshiaki; Onigata, Kazumichi; Nishi, Yoshikazu; Kato, Shigeaki; Hasegawa, Tomonobu.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 85, No. 3, 2000, p. 1290-1295.

Research output: Contribution to journalArticle

Hasegawa, Y, Fujii, K, Yamada, M, Igarashi, Y, Tachibana, K, Tanaka, T, Onigata, K, Nishi, Y, Kato, S & Hasegawa, T 2000, 'Identification of novel human GH-1 gene polymorphisms that are associated with growth hormone secretion and height', Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 3, pp. 1290-1295. https://doi.org/10.1210/jc.85.3.1290
Hasegawa, Yukihiro ; Fujii, Katsura ; Yamada, Makoto ; Igarashi, Yutaka ; Tachibana, Katsuhiko ; Tanaka, Toshiaki ; Onigata, Kazumichi ; Nishi, Yoshikazu ; Kato, Shigeaki ; Hasegawa, Tomonobu. / Identification of novel human GH-1 gene polymorphisms that are associated with growth hormone secretion and height. In: Journal of Clinical Endocrinology and Metabolism. 2000 ; Vol. 85, No. 3. pp. 1290-1295.
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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.",
author = "Yukihiro Hasegawa and Katsura Fujii and Makoto Yamada and Yutaka Igarashi and Katsuhiko Tachibana and Toshiaki Tanaka and Kazumichi Onigata and Yoshikazu Nishi and Shigeaki Kato and Tomonobu Hasegawa",
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AU - Fujii, Katsura

AU - Yamada, Makoto

AU - Igarashi, Yutaka

AU - Tachibana, Katsuhiko

AU - Tanaka, Toshiaki

AU - Onigata, Kazumichi

AU - Nishi, Yoshikazu

AU - Kato, Shigeaki

AU - Hasegawa, Tomonobu

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N2 - 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.

AB - 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.

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