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

Ye Sun; Cheng Wang; Zheng Hao; Jin Dai; Dongyang Chen; Zhihong Xu; Dongquan Shi; Ping Mao; Huajian Teng; Xiang Gao; Zhibin Hu; Hongbing Shen; Qing Jiang

doi:10.1371/journal.pone.0120212

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

PLoS One. 2015 Apr 7;10(4):e0120212. doi: 10.1371/journal.pone.0120212. eCollection 2015.

Authors

Ye Sun¹, Cheng Wang², Zheng Hao³, Jin Dai¹, Dongyang Chen³, Zhihong Xu³, Dongquan Shi¹, Ping Mao³, Huajian Teng⁴, Xiang Gao², Zhibin Hu⁵, Hongbing Shen⁵, Qing Jiang¹

Affiliations

¹ 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.
² MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
³ The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu 210008, China.
⁴ Laboratory for Bone and Joint Diseases, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, China.
⁵ Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.

Abstract

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 = 4.82*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.

Conclusion: Our study demonstrates common variants of UQCC, specifically rs6060373, are associated with DDH in Han Chinese population.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Case-Control Studies
Genetic Predisposition to Disease*
Genome-Wide Association Study
Genotype
Hip Dislocation, Congenital / genetics*
Humans
Membrane Proteins / genetics*
Odds Ratio
Polymorphism, Single Nucleotide / genetics*
Risk Factors

Substances

Membrane Proteins
UQCC1 protein, human

Grants and funding

This work was supported by China National Natural Science Funds for Youths (No. 81101338, No. 30901570) and China National Funds for Distinguished Young Scientists (No. 81125013). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.