Polymorphisms in paired box 1 gene were associated with susceptibility of adolescent idiopathic scoliosis: A case–control study

Abstract

Background Association of genetic polymorphisms in paired box 1 ( PAX-1 ) gene can influence the development of adolescent idiopathic scoliosis (AIS). PAX-1 is mainly expressed in the region of the vertebral bodies and intervertebral discs, being important for the proper formation of spinal structures. Objectives: The objective of this study was to evaluate the association of polymorphisms in PAX-1 gene with the susceptibility of AIS. Settings and Design: This was an analytical observational case–control study. Materials and Methods: Samples of 59 AIS indicated for surgical treatment, and 119 controls, without spinal disease were genotyped for PAX-1 rs6137473 and rs169311 polymorphisms. Statistical Analysis: The association of the polymorphisms with AIS was evaluated by a multivariable logistic regression model, using odds ratios (OR) and 95% confidence intervals (CI). Results: According to Lenke's classification, 89.8% had Type I and 10.2% II curves. The mean value of the Cobb angle of the proximal thoracic curve was 30.8°, 58.7° thoracic, and 30.4° for the lumbar and on the bending films 14.6°, 40.7°, and 11°, respectively. Among the AIS group, there was a predominance of females (8.8:1). The PAX-1 rs169311 and rs6137473 polymorphisms were positively associated with developing the AIS (OR = 1.98; 95% CI = 1.2–3.3 and OR = 3.16; 95% CI = 1.4–7.3, respectively). The rs6137473 polymorphism was associated with the lumbar modifier B and C compared to A (OR = 2.52; 95% CI = 1.1–5.8). Conclusions: PAX-1 polymorphisms were associated with an increased risk of developing the AIS and with curve severity and can be used as a biomarker to map the risk of developing surgical-grade AIS, guiding the treatment of patients.

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

“…The ADGRG6 gene regulates the biomechanical structure of intervertebral discs and dense connective tissues to maintain normal spinal morphology through the cAMP/CREB signaling pathway; whereas AIS patients have defective expression of the ADGRG6 gene ( 73 ). The expression of the PAX-1 gene in the disc is involved in the formation of the spinal structure ( 74 ). 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 ).…”

“…Connective tissue plays a role in maintaining normal spine morphology, including intervertebral discs, ligaments, and tendons (71,72). The ADGRG6 gene regulates the biomechanical structure of intervertebral discs and dense connective tissues to maintain normal spinal morphology through the cAMP/CREB signaling pathway; whereas AIS patients have defective expression of the ADGRG6 gene (73). The expression of the PAX-1 gene in the disc is involved in the formation of the spinal structure (74).…”

Avaliação da influência de polimorfismos nos genes da leptina e seu receptor no desenvolvimento e prognóstico da escoliose idiopática do adolescente

“…3-1.4, respectivamente). Além disso, foi observado um predomínio de pacientes com EIA com genótipo selvagem LEPR rs2767485 TT no grupo de baixo ou peso normal (≤ 24,9kg/m²) em comparação ao grupo de EIA com alto IMC (≥ 25kg/m²) (P=0,03; OR=2,48; IC95%=1, [1][2][3][4][5]8). Considerando o polimorfismo LEP rs2167270 não foi observada associação com a suscetibilidade genética da EIA (OR=0,95 e IC95%=0,75-1,2), sendo a frequência do alelo variante rs2167270 A de 35,9% nos casos e 37% nos controles (P = 0,68).…”

“…As características antropométricas dos pacientes portadores de EIA são elevada estatura, índice de massa corporal (IMC) baixo e baixa densidade óssea (CLARK et al, 2014;WATANABE et al, 2020). A etiologia da escoliose permanece desconhecida, contudo, discutese amplamente na literatura a influência e a interação de fatores hormonais, biomecânicos, genéticos e ambientais para tentar explicar o desenvolvimento e progressão da doença (BURWELL et al, 2016a;DE AZEVEDO et al, 2022;BETTANY-SALTIKOV, 2017a;MARYA et al, 2022;PEDROSA et al, 2022).…”

“…Quando ocorre a troca de um único nucleotídeo é denominado SNP (single nucleotide polymorphism). Nosso grupo tem se dedicado à busca de polimorfismos genéticos, que possam estar associados ao risco de desenvolvimento e progressão da EIA (DE AZEVEDO et al, 2022;PEDROSA et al, 2022), com intuito de entender a etiologia da doença e contribuir para identificação de um biomarcador genético que possa permitir o acompanhamento de indivíduos em risco, evitando consultas e exames radiográficos frequentes, altos custos com o tratamento e má qualidade de vida desses pacientes. A escolha de um polimorfismo candidato, se baseia no impacto do polimorfismo na expressão ou função da proteína codificada pelo respectivo gene, além da alta frequência na população alvo.…”