Evaluation of GPR50, hMel-1B, and ROR-α melatonin-related receptors and the etiology of adolescent idiopathic scoliosis

William Shyy, Kai Wang, Christina A. Gurnett, Matthew B. Dobbs, Nancy H. Miller, Carol Wise, Val C. Sheffield, Jose A. Morcuende

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity in children. Studies have shown low melatonin levels resulting from pinealectomy in chickens and mice result in the development scoliosis, whereas supplementation with melatonin after the pinealectomy prevented it. The mere characterization of low melatonin levels is not sufficient to explain the development of idiopathic scoliosis in primates and humans, but we hypothesize that a mutation in melatoninrelated receptors may be involved with the development of scoliosis. Methods: The coding, splice-site, and promoter regions of 3 melatonin-related receptors (hMel-1B, RORa, and GPR50) were evaluated by DNA sequencing for variants associated with the phenotype of adolescent idiopathic scoliosis. An initial screening of 50 scoliosis patients with adolescent idiopathic scoliosis was compared with 50 controls by DNA sequencing of the 3 receptors. Additional cases and controls were evaluated when genetic variants were observed (for a total of 885 individuals). Results: No significant differences were found in the hMel-1B and RORa receptors. We found 2 cSNPs in GPR50 (rs561077 and rs13440581) in the initial 50 patients. To evaluate the significance of these cSNPs, an additional 356 patients and 429 controls were analyzed. When the combined groups were analyzed, no significant associations were observed. Conclusions: Despite the observed relationship between melatonin and scoliosis, there is no significant association between mutations found in any known melatonin-related receptors with adolescent idiopathic scoliosis. The strong evidence of a melatonin-related cause for the development of idiopathic scoliosis still encourages research into undiscovered melatoninrelated receptors, melatonin-related hormones, and the catalytic enzymes for the serotonin-melatonin pathway. Clinical Relevance: This investigation is a genetic testing of the remaining currently known melatonin-related receptors that have not been analyzed earlier for association with AIS. Given the support in the literature of a relationship between melatonin and AIS, we have shown no mutations in any of the known melatonin-related receptor in patients with AIS.

Original languageEnglish (US)
Pages (from-to)539-543
Number of pages5
JournalJournal of Pediatric Orthopaedics
Volume30
Issue number6
DOIs
StatePublished - Sep 2010

Fingerprint

Melatonin Receptors
Scoliosis
Melatonin
DNA Sequence Analysis
Mutation
Genetic Testing
Genetic Promoter Regions
Primates

Keywords

  • Adolescent idiopathic scoliosis
  • Genetics
  • Melatonin

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Orthopedics and Sports Medicine

Cite this

Evaluation of GPR50, hMel-1B, and ROR-α melatonin-related receptors and the etiology of adolescent idiopathic scoliosis. / Shyy, William; Wang, Kai; Gurnett, Christina A.; Dobbs, Matthew B.; Miller, Nancy H.; Wise, Carol; Sheffield, Val C.; Morcuende, Jose A.

In: Journal of Pediatric Orthopaedics, Vol. 30, No. 6, 09.2010, p. 539-543.

Research output: Contribution to journalArticle

Shyy, William ; Wang, Kai ; Gurnett, Christina A. ; Dobbs, Matthew B. ; Miller, Nancy H. ; Wise, Carol ; Sheffield, Val C. ; Morcuende, Jose A. / Evaluation of GPR50, hMel-1B, and ROR-α melatonin-related receptors and the etiology of adolescent idiopathic scoliosis. In: Journal of Pediatric Orthopaedics. 2010 ; Vol. 30, No. 6. pp. 539-543.
@article{8e5ab8278eb0491da94c1b46955fc649,
title = "Evaluation of GPR50, hMel-1B, and ROR-α melatonin-related receptors and the etiology of adolescent idiopathic scoliosis",
abstract = "Background: Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity in children. Studies have shown low melatonin levels resulting from pinealectomy in chickens and mice result in the development scoliosis, whereas supplementation with melatonin after the pinealectomy prevented it. The mere characterization of low melatonin levels is not sufficient to explain the development of idiopathic scoliosis in primates and humans, but we hypothesize that a mutation in melatoninrelated receptors may be involved with the development of scoliosis. Methods: The coding, splice-site, and promoter regions of 3 melatonin-related receptors (hMel-1B, RORa, and GPR50) were evaluated by DNA sequencing for variants associated with the phenotype of adolescent idiopathic scoliosis. An initial screening of 50 scoliosis patients with adolescent idiopathic scoliosis was compared with 50 controls by DNA sequencing of the 3 receptors. Additional cases and controls were evaluated when genetic variants were observed (for a total of 885 individuals). Results: No significant differences were found in the hMel-1B and RORa receptors. We found 2 cSNPs in GPR50 (rs561077 and rs13440581) in the initial 50 patients. To evaluate the significance of these cSNPs, an additional 356 patients and 429 controls were analyzed. When the combined groups were analyzed, no significant associations were observed. Conclusions: Despite the observed relationship between melatonin and scoliosis, there is no significant association between mutations found in any known melatonin-related receptors with adolescent idiopathic scoliosis. The strong evidence of a melatonin-related cause for the development of idiopathic scoliosis still encourages research into undiscovered melatoninrelated receptors, melatonin-related hormones, and the catalytic enzymes for the serotonin-melatonin pathway. Clinical Relevance: This investigation is a genetic testing of the remaining currently known melatonin-related receptors that have not been analyzed earlier for association with AIS. Given the support in the literature of a relationship between melatonin and AIS, we have shown no mutations in any of the known melatonin-related receptor in patients with AIS.",
keywords = "Adolescent idiopathic scoliosis, Genetics, Melatonin",
author = "William Shyy and Kai Wang and Gurnett, {Christina A.} and Dobbs, {Matthew B.} and Miller, {Nancy H.} and Carol Wise and Sheffield, {Val C.} and Morcuende, {Jose A.}",
year = "2010",
month = "9",
doi = "10.1097/BPO.0b013e3181e7902c",
language = "English (US)",
volume = "30",
pages = "539--543",
journal = "Journal of Pediatric Orthopaedics",
issn = "0271-6798",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Evaluation of GPR50, hMel-1B, and ROR-α melatonin-related receptors and the etiology of adolescent idiopathic scoliosis

AU - Shyy, William

AU - Wang, Kai

AU - Gurnett, Christina A.

AU - Dobbs, Matthew B.

AU - Miller, Nancy H.

AU - Wise, Carol

AU - Sheffield, Val C.

AU - Morcuende, Jose A.

PY - 2010/9

Y1 - 2010/9

N2 - Background: Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity in children. Studies have shown low melatonin levels resulting from pinealectomy in chickens and mice result in the development scoliosis, whereas supplementation with melatonin after the pinealectomy prevented it. The mere characterization of low melatonin levels is not sufficient to explain the development of idiopathic scoliosis in primates and humans, but we hypothesize that a mutation in melatoninrelated receptors may be involved with the development of scoliosis. Methods: The coding, splice-site, and promoter regions of 3 melatonin-related receptors (hMel-1B, RORa, and GPR50) were evaluated by DNA sequencing for variants associated with the phenotype of adolescent idiopathic scoliosis. An initial screening of 50 scoliosis patients with adolescent idiopathic scoliosis was compared with 50 controls by DNA sequencing of the 3 receptors. Additional cases and controls were evaluated when genetic variants were observed (for a total of 885 individuals). Results: No significant differences were found in the hMel-1B and RORa receptors. We found 2 cSNPs in GPR50 (rs561077 and rs13440581) in the initial 50 patients. To evaluate the significance of these cSNPs, an additional 356 patients and 429 controls were analyzed. When the combined groups were analyzed, no significant associations were observed. Conclusions: Despite the observed relationship between melatonin and scoliosis, there is no significant association between mutations found in any known melatonin-related receptors with adolescent idiopathic scoliosis. The strong evidence of a melatonin-related cause for the development of idiopathic scoliosis still encourages research into undiscovered melatoninrelated receptors, melatonin-related hormones, and the catalytic enzymes for the serotonin-melatonin pathway. Clinical Relevance: This investigation is a genetic testing of the remaining currently known melatonin-related receptors that have not been analyzed earlier for association with AIS. Given the support in the literature of a relationship between melatonin and AIS, we have shown no mutations in any of the known melatonin-related receptor in patients with AIS.

AB - Background: Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity in children. Studies have shown low melatonin levels resulting from pinealectomy in chickens and mice result in the development scoliosis, whereas supplementation with melatonin after the pinealectomy prevented it. The mere characterization of low melatonin levels is not sufficient to explain the development of idiopathic scoliosis in primates and humans, but we hypothesize that a mutation in melatoninrelated receptors may be involved with the development of scoliosis. Methods: The coding, splice-site, and promoter regions of 3 melatonin-related receptors (hMel-1B, RORa, and GPR50) were evaluated by DNA sequencing for variants associated with the phenotype of adolescent idiopathic scoliosis. An initial screening of 50 scoliosis patients with adolescent idiopathic scoliosis was compared with 50 controls by DNA sequencing of the 3 receptors. Additional cases and controls were evaluated when genetic variants were observed (for a total of 885 individuals). Results: No significant differences were found in the hMel-1B and RORa receptors. We found 2 cSNPs in GPR50 (rs561077 and rs13440581) in the initial 50 patients. To evaluate the significance of these cSNPs, an additional 356 patients and 429 controls were analyzed. When the combined groups were analyzed, no significant associations were observed. Conclusions: Despite the observed relationship between melatonin and scoliosis, there is no significant association between mutations found in any known melatonin-related receptors with adolescent idiopathic scoliosis. The strong evidence of a melatonin-related cause for the development of idiopathic scoliosis still encourages research into undiscovered melatoninrelated receptors, melatonin-related hormones, and the catalytic enzymes for the serotonin-melatonin pathway. Clinical Relevance: This investigation is a genetic testing of the remaining currently known melatonin-related receptors that have not been analyzed earlier for association with AIS. Given the support in the literature of a relationship between melatonin and AIS, we have shown no mutations in any of the known melatonin-related receptor in patients with AIS.

KW - Adolescent idiopathic scoliosis

KW - Genetics

KW - Melatonin

UR - http://www.scopus.com/inward/record.url?scp=78650038224&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650038224&partnerID=8YFLogxK

U2 - 10.1097/BPO.0b013e3181e7902c

DO - 10.1097/BPO.0b013e3181e7902c

M3 - Article

VL - 30

SP - 539

EP - 543

JO - Journal of Pediatric Orthopaedics

JF - Journal of Pediatric Orthopaedics

SN - 0271-6798

IS - 6

ER -