1. 2015;18;419-431The Association of rs4753426 Polymorphism in the Melatonin Receptor 1B (MTNR1B) Gene and Susceptibility to Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-analysis
   Systematic Review
   Hao Liu, MD, Peng Yang, MD, Jun Lin, MD, PhD, and Huilin Yang, MD.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a tridimensional structural deformity of the spine that may deteriorate progressively, leading to significant functional limitations and pain problems. Several previous studies have implicated the rs4753426 single nucleotide polymorphism in the melatonin receptor 1B (MTNR1B) gene in the etiology of AIS. However the sample sizes were limited and the findings of those studies were inconsistent. An overall assessment of the evidence supporting this association has not been previously conducted.

OBJECTIVES: To provide a comprehensive assessment and synthesis of the currently available evidence on the association between rs4753426 and AIS.

STUDY DESIGN: A systematic review and meta-analysis.

SETTING: University hospital, China.

METHODS: This review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. PubMed (MEDLINE), EMBASE, Scopus databases, and WANFANG databases were systematically searched through December 2014 to identify relevant studies following a sensitive strategy. Statistical analysis was performed using the Review Manager 5.2 software. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using the fixed-effect inverse variance model for allelic (C vs. T) and genotypic comparisons.

RESULTS: Four papers including 5 studies which involved 2,552 AIS cases and 2,738 controls were identified for this meta-analysis. The results showed that C allele of the rs4753426 was significantly associated with AIS (OR = 1.12, 95% CI: 1.03 – 1.21, P = 0.01). CT and CC genotypes were 26% (OR = 1.26, 95% CI: 1.04 – 1.53, P = 0.01) and 28% (OR = 1.28, 95% CI: 1.05 – 1.56, P = 0.01), respectively, more likely to have AIS compared with CC genotype. As for the dominant model (CC+TT vs. TT), summary ORs showed statistically significant association with AIS (OR = 1.28, 95% CI: 1.06 – 1.53, P = 0.009). Compared with the CT+TT genotype, the summary ORs of the CC genotype showed marginally statistically significant association with AIS (OR = 1.11, 95 % CI: 0.99 – 1.24, P = 0.07). The subgroup meta-analysis results showed the C allele and each genotype were significantly associated with AIS in the Asian group but not in the Caucasian group.

LIMITATIONS: Paucity of available literature.

CONCLUSIONS: To our knowledge, there has been no meta-analysis to analyze the association between rs4753426 polymorphism in the MTNR1B gene and AIS. This systematic review was a comprehensive analysis of the currently available evidence, and found an overall significant association of rs4753426 polymorphism with the risk of AIS, especially in the Asian population. Further investigation of this association is necessary in other populations.