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Genome-wide association study identifies ITPR2 as a susceptibility gene for Kashin-Beck disease in Han Chinese.
Arthritis Rheumatol. 2015 Jan; 67(1):176-81.AR

Abstract

OBJECTIVE

Kashin-Beck disease (KBD) is a chronic osteochondropathy, the pathogenesis of which remains elusive. The aim of this study was to identify susceptibility genes for KBD by conducting a 2-stage genome-wide association study (GWAS).

METHODS

Ninety patients with grade II or grade III KBD with extreme KBD phenotypes and 1,627 healthy control subjects were enrolled in the initial GWAS. Affymetrix Genome-Wide Human SNP Array 6.0 was used for genotyping. For the replication study, 9 single-nucleotide polymorphisms (SNPs) of the significant gene identified by the GWAS (ITPR2) were tested in an independent validation sample composed of 559 patients with KBD and 467 healthy control subjects.

RESULTS

The GWAS identified significant association (P = 1.58 × 10(-8)) between KBD and a novel locus, ITPR2 SNP rs10842750. The replication study showed significant associations with KBD at 9 ITPR2 SNPs, including rs10842750 (P = 5.97 × 10(-3)), rs16931011 (P = 1.29 × 10(-3)), rs1531928 (P = 4.95 × 10(-3)), rs4414322 (P = 4.40 × 10(-3)), rs11048570 (P = 4.53 × 10(-3)), rs11048572 (P = 4.43 × 10(-3)), rs2017510 (P = 4.58 × 10(-3)), rs9669395 (P = 5.77 × 10(-3)), and rs1002835 (P = 4.85 × 10(-3)). In patients with KBD, the genotype score for rs10842750 was also correlated with KBD clinical severity grades (P = 0.013).

CONCLUSION

Our results strongly suggest that ITPR2 is a novel susceptibility gene for KBD in Han Chinese. This study may provide new insights into the pathogenesis and rationale for treatment of KBD as well as other osteoarthritides with similar articular cartilage lesions.

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Publisher Full Text

Authors+Show Affiliations

Zhang F
Xi'an Jiaotong University, Xi'an, China.
Wen Y
No affiliation info available
Guo X
No affiliation info available
Zhang Y
No affiliation info available
Wang X
No affiliation info available
Yang T
No affiliation info available
Shen H
No affiliation info available
Chen X
No affiliation info available
Tian Q
No affiliation info available
Deng HW
No affiliation info available

MeSH

AdultAgedAsian Continental Ancestry GroupCase-Control StudiesChinaFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansInositol 1,4,5-Trisphosphate ReceptorsKashin-Beck DiseaseMaleMiddle AgedPolymorphism, Single NucleotideSeverity of Illness Index

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25303641

Citation

Zhang, Feng, et al. "Genome-wide Association Study Identifies ITPR2 as a Susceptibility Gene for Kashin-Beck Disease in Han Chinese." Arthritis & Rheumatology (Hoboken, N.J.), vol. 67, no. 1, 2015, pp. 176-81.
Zhang F, Wen Y, Guo X, et al. Genome-wide association study identifies ITPR2 as a susceptibility gene for Kashin-Beck disease in Han Chinese. Arthritis & rheumatology (Hoboken, N.J.). 2015;67(1):176-81.
Zhang, F., Wen, Y., Guo, X., Zhang, Y., Wang, X., Yang, T., Shen, H., Chen, X., Tian, Q., & Deng, H. W. (2015). Genome-wide association study identifies ITPR2 as a susceptibility gene for Kashin-Beck disease in Han Chinese. Arthritis & Rheumatology (Hoboken, N.J.), 67(1), 176-81. https://doi.org/10.1002/art.38898
Zhang F, et al. Genome-wide Association Study Identifies ITPR2 as a Susceptibility Gene for Kashin-Beck Disease in Han Chinese. Arthritis & rheumatology (Hoboken, N.J.). 2015;67(1):176-81. PubMed PMID: 25303641.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genome-wide association study identifies ITPR2 as a susceptibility gene for Kashin-Beck disease in Han Chinese. AU - Zhang,Feng, AU - Wen,Yan, AU - Guo,Xiong, AU - Zhang,Yingang, AU - Wang,Xi, AU - Yang,Tielin, AU - Shen,Hui, AU - Chen,Xiangding, AU - Tian,Qing, AU - Deng,Hong-Wen, PY - 2014/04/09/received PY - 2014/09/25/accepted PY - 2014/10/11/entrez PY - 2014/10/11/pubmed PY - 2015/3/31/medline SP - 176 EP - 81 JF - Arthritis & rheumatology (Hoboken, N.J.) VL - 67 IS - 1 N2 - OBJECTIVE: Kashin-Beck disease (KBD) is a chronic osteochondropathy, the pathogenesis of which remains elusive. The aim of this study was to identify susceptibility genes for KBD by conducting a 2-stage genome-wide association study (GWAS). METHODS: Ninety patients with grade II or grade III KBD with extreme KBD phenotypes and 1,627 healthy control subjects were enrolled in the initial GWAS. Affymetrix Genome-Wide Human SNP Array 6.0 was used for genotyping. For the replication study, 9 single-nucleotide polymorphisms (SNPs) of the significant gene identified by the GWAS (ITPR2) were tested in an independent validation sample composed of 559 patients with KBD and 467 healthy control subjects. RESULTS: The GWAS identified significant association (P = 1.58 × 10(-8)) between KBD and a novel locus, ITPR2 SNP rs10842750. The replication study showed significant associations with KBD at 9 ITPR2 SNPs, including rs10842750 (P = 5.97 × 10(-3)), rs16931011 (P = 1.29 × 10(-3)), rs1531928 (P = 4.95 × 10(-3)), rs4414322 (P = 4.40 × 10(-3)), rs11048570 (P = 4.53 × 10(-3)), rs11048572 (P = 4.43 × 10(-3)), rs2017510 (P = 4.58 × 10(-3)), rs9669395 (P = 5.77 × 10(-3)), and rs1002835 (P = 4.85 × 10(-3)). In patients with KBD, the genotype score for rs10842750 was also correlated with KBD clinical severity grades (P = 0.013). CONCLUSION: Our results strongly suggest that ITPR2 is a novel susceptibility gene for KBD in Han Chinese. This study may provide new insights into the pathogenesis and rationale for treatment of KBD as well as other osteoarthritides with similar articular cartilage lesions. SN - 2326-5205 UR - https://www.unboundmedicine.com/medline/citation/25303641/Genome_wide_association_study_identifies_ITPR2_as_a_susceptibility_gene_for_Kashin_Beck_disease_in_Han_Chinese_ L2 - https://doi.org/10.1002/art.38898 DB - PRIME DP - Unbound Medicine ER -