泛醇 - 细胞色素c还原酶复合物的一种常见变体与发育性髋关节发育不良有关。
A common variant of ubiquinol-cytochrome c reductase complex is associated with DDH.
作者信息
Sun Ye, Wang Cheng, Hao Zheng, Dai Jin, Chen Dongyang, Xu Zhihong, Shi Dongquan, Mao Ping, Teng Huajian, Gao Xiang, Hu Zhibin, Shen Hongbing, Jiang Qing
机构信息
The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu 210008, China; Laboratory for Bone and Joint Diseases, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
出版信息
PLoS One. 2015 Apr 7;10(4):e0120212. doi: 10.1371/journal.pone.0120212. eCollection 2015.
PURPOSE
Genetic basis of Developmental dysplasia of the hip (DDH) remains largely unknown. To find new susceptibility genes for DDH, we carried out a genome-wide association study (GWAS) for DDH.
METHODS
We enrolled 386 radiology confirmed DDH patients and 558 healthy controls (Set A) to conduct a genome-wide association study (GWAS). Quality-control was conducted at both the sample and single nucleotide polymorphism (SNP) levels. We then conducted a subsequent case-control study to replicate the association between a promising loci, rs6060373 in UQCC gene and DDH in an independent set of 755 cases and 944 controls (set B).
RESULTS
In the DDH GWAS discovering stage, 51 SNPs showed significance of less than 10-4, and another 577 SNPs showed significance of less than 10-3. In UQCC, all the 12 genotyped SNPs showed as promising risk loci. Genotyping of rs6060373 in set A showed the minor allele A as a promising risk allele (p = 4.8210-7). In set A, the odds ratio of allele A was 1.77. Genotyping of rs6060373 in Set B produced another significant result (p = 0.0338) with an odds ratio of 1.18 for risk allele A. Combining set A and set B, we identified a total p value of 3.6310-6 with the odds ratio of 1.35 (1.19-1.53) for allele A.
CONCLUSION
Our study demonstrates common variants of UQCC, specifically rs6060373, are associated with DDH in Han Chinese population.
目的
髋关节发育不良（DDH）的遗传基础在很大程度上仍不清楚。为了寻找DDH的新易感基因，我们开展了一项针对DDH的全基因组关联研究（GWAS）。
方法
我们纳入了386例经放射学确诊的DDH患者和558例健康对照（A组）进行全基因组关联研究（GWAS）。在样本和单核苷酸多态性（SNP）水平上进行质量控制。然后我们进行了一项后续病例对照研究，以在另一组755例病例和944例对照（B组）中重复验证UQCC基因中一个有前景的位点rs6060373与DDH之间的关联。
结果
在DDH的GWAS发现阶段，51个SNP显示出小于10-4的显著性，另外577个SNP显示出小于10-3的显著性。在UQCC基因中，所有12个基因分型的SNP均显示为有前景的风险位点。A组中rs6060373的基因分型显示次要等位基因A为有前景的风险等位基因（p = 4.82×10-7）。在A组中，等位基因A的比值比为1.77。B组中rs6060373的基因分型产生了另一个显著结果（p = 0.0338），风险等位基因A的比值比为1.18。将A组和B组合并，我们确定等位基因A的总p值为3.63×10-6，比值比为1.35（1.19 - 1.53）。
结论
我们的研究表明，UQCC的常见变异，特别是rs6060373，与中国汉族人群的DDH相关。
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