Sadat-Ali Mir, Al-Habdan Ibrahim M, Bubshait Dalal A
College of Medicine, Imam AbdulRahman Bin Faisal University, Dammam, Saudi Arabia.
King Fahd Hospital of the University, P.O. Box 40071, Al Khobar, 31952, Saudi Arabia.
Biochem Genet. 2018 Dec;56(6):618-626. doi: 10.1007/s10528-018-9864-7. Epub 2018 May 23.
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.
髋关节发育不良（DDH）在沙特阿拉伯婴儿中相当常见。为了评估DDH患者、其父母以及未受影响的兄弟姐妹中GDF5基因单核苷酸多态性（SNP）rs143383及其等位基因的存在情况，我们开展了这项病例对照研究。我们收集并分析了GDF5基因5'非翻译区的一个功能性单核苷酸多态性（SNP）（rs143383），共473份血样（100例患者、200名父母、73名兄弟姐妹和100名健康对照）。我们通过卡方分析确定了患者基因型与其父亲、母亲和兄弟姐妹基因型之间的关联。大多数被筛查者具有TC基因型，61.8%的患者及其父亲具有TT基因型。患者与父亲的基因型之间无关联，P值<0.332，95%置信区间（0.328 - 0.346），患者与母亲的基因型之间也无关联，P<0.006，95%置信区间（0.004 - 0.007）。在考虑DDH患者和对照组的基因型时，TT与其他组合相比的优势比（0.641>1）以及CC与其他组合相比的优势比（0.474<1）表明，与CC基因型相比，TT基因型患DDH的风险更高。TT与其他组合以及CC与其他组合的95%置信区间分别为0.932 - 2.891和0.208 - 1.078。对于患者与父亲的基因型，TT与其他组合相比的优势比（1.275>1）以及CC与其他组合相比的优势比（0.815<1）表明，与CC基因型相比，TT基因型表现出DDH的风险更高。对于患者与兄弟姐妹的基因型，TT与其他组合相比的优势比（1.669）以及CC与其他组合相比的优势比（1.048）表明，与CC基因型相比，TT基因型患DDH的风险更高。我们的研究表明，在我们的人群中GDF5（SNP rs143383）与DDH之间存在关联。其次，我们首次发现基因型TT和T等位基因在患者及其父亲中过度表达。需要更多研究来证实这种DDH的遗传标记。
