A common variant of ubiquinol-cytochrome c reductase complex is associated with DDH

• Published in: PloS one 2015-04, Vol.10 (4), p.e0120212-e0120212
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Alleles; Arthritis; Case-Control Studies; Cell growth; Cytochrome; Cytochrome c; Disease; Disease susceptibility; Dysplasia; Electron transport; Epidemiology; Fibroblasts; Genes; Genetic aspects; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Genotype; Genotyping; Growth factors; Hip; Hip Dislocation, Congenital - genetics; Hospitals; Humans; Laboratories; Loci; Medical diagnosis; Medical schools; Membrane Proteins - genetics; Odds Ratio; Polymorphism; Polymorphism, Single Nucleotide - genetics; Public health; Radiology; Reductase; Risk; Risk Factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Ubiquinol
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0120212

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. 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). 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 = 4.82*10-7). 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 3.63*10-6 with the odds ratio of 1.35 (1.19-1.53) for allele A. Our study demonstrates common variants of UQCC, specifically rs6060373, are associated with DDH in Han Chinese population.