Association of single-nucleotide polymorphisms in HLA class II/III region with knee osteoarthritis

Shi, D.; Zheng, Q.; Chen, D.; Zhu, L.; Qin, A.; Fan, J.; Liao, J.; Xu, Z.; Lin, Z.; Norman, P.; Xu, J.; Nakamura, T.; Dai, K.; Zheng, M.; Jiang, Q.

doi:10.1016/j.joca.2010.07.009

« Previous Next »Osteoarthritis and Cartilage
Volume 18, Issue 11 , Pages 1454-1457, November 2010

Association of single-nucleotide polymorphisms in HLA class II/III region with knee osteoarthritis

D. Shi
- The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, Jiangsu, China
- Australia-China Joint Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University, Nanjing 210093, China
- These authors contributed equally to this work.
Q. Zheng
- Division of Orthopaedic Surgery, Department of Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, PR China
- These authors contributed equally to this work.
D. Chen
- The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, Jiangsu, China
L. Zhu
- The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, Jiangsu, China
A. Qin
- Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Cawley WA 6009, Australia
- Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, PR China
J. Fan
- The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, Jiangsu, China
J. Liao
- Division of Orthopaedic Surgery, Department of Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, PR China
Z. Xu
- The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, Jiangsu, China
Z. Lin
- Division of Orthopaedic Surgery, Department of Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, PR China
P. Norman
- School of Surgery at Fremental Hospital, The University of Western Australia, Cawley WA 6009, Australia
J. Xu
- Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Cawley WA 6009, Australia
T. Nakamura
- Laboratory for Mathematics, National Defense Medical College, Saitama 359-8513, Japan
K. Dai
- Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, PR China
M. Zheng
- Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Cawley WA 6009, Australia
- Address correspondence and reprint requests to: Minghao Zheng, Orthopaedic Surgery (Centre for Orthopaedic Research), The University of Western Australia (M508), Crawley WA 6009, Australia. Tel: 61-93464050; Fax: 61-93463210.
Q. Jiang
- The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, Jiangsu, China
- Australia-China Joint Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University, Nanjing 210093, China
- Address correspondence and reprint requests to: Qing Jiang, The Center of Diagnosis and Treatment for Joint Disease, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Zhongshan Road 321, Nanjing 210008, Jiangsu, China. Tel: 86-25-83107008; Fax: 86-25-83317016.

Received 8 April 2010; accepted 20 July 2010. published online 06 August 2010.

Summary

Objective

A genome-wide association study and a replication using Japanese, Spanish and Greek Caucasian populations have recently indicated two single-nucleotide polymorphisms (SNPs) (rs7775228 and rs10947262) associated with knee Osteoarthritis (OA) susceptibility. We have further evaluated the association in knee OA subjects from Han Chinese and Australian Caucasian origin.

Methods

Two independent case-control association studies were performed using Han Chinese and Australian Caucasian populations. The two SNPs were genotyped in patients who had primary symptomatic knee OA with radiographic confirmation and/or received total knee replacement surgery as well as in matched controls. They were subjected to statistic analyses.

Results

A total of 991 OA patients and 1536 controls were genotyped. No significant difference was detected in genotype or allele frequencies of the two SNPs between knee OA and control groups in the two populations (all P>0.05). The association was also negative even after stratification by sex, body mass index (BMI) and Kellgren/Lawrence scores. The significant heterogeneity was detected between Chinese and Japanese (both P<0.05). In the Caucasian samples, no significant heterogeneity was detected (both P>0.05). The result of meta-analysis showed significant association between knee OA and rs10947262 in total subjects [summary OR=1.26, 95%confidence intervals (CI)=1.07–1.27, P=3×10⁻⁸] and in Caucasian samples (summary OR=1.28, 95%CI=1.04–1.57, P=0.02).

Conclusion

We demonstrated no association between the two SNPs in human leukocyte antigen (HLA) class II/III region and knee OA in Han Chinese population. A significant association was detected between SNP rs10947262 and knee OA in Caucasian subjects. Further replication studies are required to identify the impact of controversial association.

Keywords: Knee osteoarthritis, Single-nucleotide polymorphism, Case-control study