Genetic Influence in Developmental Dysplasia of the Hip in Saudi Arabian Children Due to GDF5 Polymorphism

Abstract

Developmental dysplasia of the hip (DDH) is quite common among Saudi Arabian babies. With an objective to assess the presence of SNP rs143383 and the alleles in the GDF5 gene among patients with DDH, parents, and unaffected siblings, we undertook this case-controlled study. We collected and analyzed for a functional single nucleotide polymorphism (SNP) in the 5'-untranslated region of the GDF5 gene (rs143383), 473 blood samples, (100 patients, 200 parents, 73 siblings and 100 healthy controls. We determined the association between the patients' genotype and their fathers', mothers' and siblings' genotype through Chi-square analysis. The majority of those screened possessed the TC genotype, and 61.8% of patients and their fathers had the TT genotype. There was no association between patients' and fathers' genotype, P value < 0.332, 95% CI (0.328-0.346), and between patients' and mothers', P < 0.006, 95% CI (0.004-0.007). When considering DDH patients' and the control group's genotypes, the odds ratios of TT versus other combined (0.641 > 1) and CC versus other combined (0.474 < 1) revealed that the TT genotype has higher risk of developing DDH compared with the CC genotype. The 95 percent confidence interval of TT versus other combined and CC versus other combined is 0.932-2.891 and 0.208-1.078, respectively. For patients' and fathers' genotypes, the odds ratios of TT versus other combined (1.275 > 1) and CC versus other combined (0.815 < 1) indicate that the TT genotype has higher risk of exhibiting DDH compared to the CC genotype. For patients' and siblings' genotypes, the odds ratios of TT versus other combined (1.669) and CC versus other combined (1.048) specify that the TT genotype possesses higher risk of developing DDH compared with the CC genotype. Our study shows that there exists a relationship between GDF5 (SNP rs143383) and DDH in our population. Second, we found for the first time that the genotype TT and the T allele were overly expressed in the patients and the fathers. More studies on the confirmation of this genetic marker for DDH are called for.

Assessment of Community Levels of Knowledge About Developmental Dysplasia of the Hip, its Risk Factors, Treatment, and Complications in the Riyadh Region, Saudi Arabia

“…Additionally, the Saudi population had a genetic link between GDF5 (SNP rs143383) and DDH. Furthermore, the genotype TT and the T allele were over-expressed in the patients and their fathers [7].…”

The association of growth differentiation factor 5 rs143383 gene polymorphism with osteoarthritis: a systematic review and meta-analysis

“…The genes displaying the most statistically significant co-expression link to GDF5. A specific polymorphism in GDF5 has been linked to DDH, and DDH patients more frequently carry the T allele [ 6 , 34 , 35 ]. This may be closely related to the occurrence and development of OA, possibly through the same mechanism.…”

Whole exome sequencing of 28 families of Danish descent reveals novel candidate genes and pathways in developmental dysplasia of the hip

“…Until now, 34 genes have been related to DDH in humans (Mabuchi et al 2006 ; Kapoor et al 2007 ; Dai et al 2008 ; Rouault et al 2010 ; Wang et al 2010 ; Shi et al 2011 ; Jia et al 2012 ; Tian et al 2012 ; Feldman et al 2013 , 2019 ; Sekimoto et al 2013 ; Tuzovic et al 2013 ; Zhao et al 2013 , 2017 ; Hao et al 2014 ; Liu et al 2014 ; Cengic et al 2015 ; Sun et al 2015 ; Watson et al 2015 ; Basit et al 2017 , 2018 ; Li et al 2017 ; Ma et al 2017 ; Qiao et al 2017 ; Hatzikotoulas et al 2018 ; Sadat-Ali et al 2018 ; Zhang et al 2018 ; Zhu et al 2019 ; Harsanyi et al 2020a ; Kenanidis et al 2020 ), sometimes with contradictory results (Rubini et al 2008 ). However, no tight phenotype–genotype correlations have been established and the molecular mechanisms of the disease have just started to be elucidated.…”