Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis.
METHODS
A genetic association study to comprehensively investigate variations of melatonin receptor 1B gene polymorphism by a set of tagging single nucleotide polymorphisms (tagSNPs) derived from the International Hapmap project.


OBJECTIVE
To determine whether melatonin receptor 1B (MTNR1B) gene polymorphisms are associated with the predisposition and/or disease severity of adolescent idiopathic scoliosis (AIS).


BACKGROUND
Linkage studies suggested a genetic predisposition for AIS. In addition, evidence showed that AIS might be related to melatonin deficiency and dysfunction of melatonin signaling pathway. Locating in one of the chromosomal regions linked to AIS, MTNR1B gene is a potential candidate gene for AIS.


METHODS
This study was carried out in 2-stage case-control analysis: 1) initial screening (472 cases and 304 controls) and 2) separate replication test (342 cases and 347 controls) to confirm results in the screening. In the first screening stage, 5 tagSNPs were selected to cover most of the genetic variation in the MTNR1B gene. In the second stage, SNPs showing association in the screening stage were studied in a separate replication sample set to confirm the association. Genotyping was performed by PCR-RFLP.


RESULTS
The first stage showed a putative association between rs4753426 and AIS, which was confirmed in the replication sample set. By meta-analysis, the frequency of C allele of this SNP locating in the promoter was significantly higher in the cases than controls (P = 0.006 aftermeta-analysis). Subjects with the CC genotype had an odds ratio of 1.29 for AIS. Another SNP rs741837 in promoter region, being moderate linkage disequilibrium with rs4753426, was also marginally associated with AIS.


CONCLUSIONS
Polymorphisms of the promoter of MTNR1B gene were associated with AIS, but not with the curve severity in AIS patients. This suggested that MTNR1B was an AIS predisposition gene.
Qiu
Xu Sheng
XS
Department of Orthopaedics and Traumatology, Chinese University of Hong Kong, China.
Tang
Nelson L S
NL
Yeung
Hiu Yan
HY
Lee
Kwong-Man
KM
Hung
Vivian W Y
VW
Ng
Bobby K W
BK
Ma
Suk Ling
SL
Kwok
Rachel H K
RH
Qin
Lin
L
Qiu
Yong
Y
Cheng
Jack C Y
JC
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D044123:Receptor, Melatonin, MT2 / Q000235:genetics*; D012600:Scoliosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology
D005819:Genetic Markers; D044123:Receptor, Melatonin, MT2