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, while 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 melatonin-related receptors may be involved with the development of scoliosis.

Polygenic Threshold Model with Sex Dimorphism in Adolescent Idiopathic Scoliosis: The Carter Effect

“…Additional reported linkage peaks for AIS include regions on chromosomes 6, 9, 16, and 17 15 , as well as 18q in a single family with both pectus excavatum and AIS 16 . In addition to identifying areas of linkage, several studies have provided support for different candidate genes 17 including melatonin-related receptors 18 and estrogen receptors 19,20 . The results of recently reported genome-wide association studies also suggest that AIS is weakly to modestly associated with dozens if not hundreds of common polymorphisms across the genome 21,22 .…”

Abnormal Skeletal Growth in Adolescent Idiopathic Scoliosis Is Associated with Abnormal Quantitative Expression of Melatonin Receptor, MT2

“…It is likely that this polymorphism could affect the gene expression of MT2, thus accounting for the lower mRNA expression level of MT2 found in AIS patients in the current study. The results of Qiu’s study could not be reproduced by a few related studies [53–56], which might partly be explained by the different ethnic populations [54–56] recruited for the studies. It is recognized that the ratio of combinations of the SNP of interest is different among different ethnic groups (Hapmap).…”

“…In the study of Shyy et al . [53], only 180 AIS patients and 180 normal controls were recruited, a much smaller number than the sample size of 814 AIS patients and 651 controls used in the study of Qiu et al . [47].…”

Higher Levels of Melatonin in Early Stages of Adolescent Idiopathic Scoliosis

“…[16][17][18] Several genetic studies failed to identify mutations in the genes responsible for the production of melatonin. [19][20][21][22][23][24] There is only one study suggesting that the MTNR1B gene responsible for a melatonin receptor is a predisposing factor for the development of AIS. 25 Recent studies focus on the role of Gi proteins on the cellular membrane, which are in contact with the melatonin receptors and play an important role in the phosphorylation of other cell proteins, such as protein kinase A and C. The role of Gi proteins seems to be crucial, leading to a transmembrane dysfunction, which in turn affects the transfer of the melatonin hormonal message inside the cell by altering c-AMP levels.…”