Association of FBN1 polymorphism with susceptibility of adolescent idiopathic scoliosis: a case-control study

Abstract

Background Fibrillin-1 (FBN1) is an extracellular matrix glycoprotein essential to the structural component of microfibrils and FBN1 gene polymorphisms can be associated with adolescent idiopathic scoliosis (AIS) susceptibility. This study aimed to evaluate the potential role of the FBN1 rs12916536 polymorphism in AIS development or severity and the variation in Cobb angle in relation to patient’s characteristics. Methods DNA from 563 subjects (185 AIS patients and 378 controls) were genotyped using a validated TaqMan allelic discrimination assay. A multivariate logistic regression model evaluated the association between polymorphism and AIS, using the adjusted odds ratios (OR) with their respective 95% confidence intervals (95% CI). A linear regression analysis evaluated the variation in Cobb angle according to the patient’s age and body mass index (BMI). Results Among the AIS group there was a predominance of females (12:1), low or normal BMI (90%), 58% had a Cobb angle greater than 45° and 74% were skeletally mature. Age was a risk factor (4-fold) for curve progression higher than BMI (P < 0.001). The allelic frequency of the rs12916536 G > A polymorphism was 40% in controls and 31% in AIS cases; and this difference was statistically significant (P = 0.004). FBN1 rs12916536 GA + AA genotypes were associated with a lower risk of AIS susceptibility (OR = 0.58 and 95% CI = 0.35–0.98), after adjustment for age, sex and BMI. However, no significant differences were detected in polymorphism distribution with the severity of the disease (Cobb < 45° or ≥ 45°). Conclusion Age was a risk factor for progression of the scoliotic curve and FBN1 rs12916536 polymorphism a protective factor for AIS susceptibility.

Single Nucleotide Polymorphisms and Adolescent Idiopathic Scoliosis

“…Based on the inclusion and exclusion criteria set initially, out of the initial 690 papers extracted, 126 duplicate papers were removed. After the first inclusion/exclusion process 62 papers were considered for full-text review, from which 43 papers with 19412 cases, 22005 controls and 25 different genes were included in the final analysis14–54 (Figure 1). All excluded studies are presented in Supplemental Table 1 (Supplemental Digital Content 1, http://links.lww.com/BRS/C34).…”

Advances in genetic factors of adolescent idiopathic scoliosis: a bibliometric analysis

“…In addition, upregulation of ERC2 and MAFB gene expression in AIS patients may promote hypertrophy of the ligamentum flavum to adapt to mechanical stresses generated by scoliosis via the TGF-β pathway ( 75 ). The FBN1 gene is crucial for connective tissue function ( 76 ), and its low expression reduces the synthesis of extracellular matrix proteins, which is detrimental to maintaining the stability of the biomechanical structure of connective tissues such as ligaments and intervertebral discs, leading to the progression of AIS ( 77 ). ADAMTSL2 and LTBPs can bind to FBN1 in vitro and upregulate the TGF-β signaling pathway in fibroblasts ( 78 – 81 ).…”

Sex differences in musculoskeletal injury and disease risks across the lifespan: Are there unique subsets of females at higher risk than males for these conditions at distinct stages of the life cycle?

“…To address some of the gaps, a number of studies and reviews have explored and analyzed the possibility that there are genetic or epigenetic-related variables at play in disease initiation and progression ( Gorman et al, 2012 ; Zaydman et al, 2021 ; De Salvatore et al, 2022 ; Faldini et al, 2022 ). A number of studies have implicated a variety of genes and gene families in AIS including Fibrillin-1 ( Sheng et al, 2019 ; De Azevedo et al, 2022 ), Fibrillin-1 and Fibrillin-2 variants associated with severe disease ( Buchan et al, 2014 ), estrogen receptor variants and polymorphisms ( Esposito et al, 2009 ; Wang et al, 2020 ), the NUCKS1 gene in Chinese adolescents ( Xu et al, 2017 ), and the helicase DNA-binding protein 7 (CHD7) ( Wu et al, 2021 ; Wu et al, 2022 ). While additional studies are needed in this area, the heterogeneity in genetic contributions detected thus far may indicate that the term AIS is an umbrella term for multiple subsets of the disease, or more information is needed to better understand the molecular basis for a common set of pathways.…”