Association Between EN1 Rs4144782 and Susceptibility of Knee Osteoarthritis: A Case-control Study

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Apr 22

PMID 28430581

Citations 4

Authors

Haohuan Li

Xiaolong Zhang

Yiping Cao

Song Hu

Fei Peng

Jianlin Zhou

Jianping Li

Affiliations

Soon will be listed here.

Abstract

Osteoarthritis (OA) is a complex disease that affects the whole joint, resulting from the combined influence of biomechanical factors and genetic factors. The heritable component for primary OA accounts for about 60% of variation in population liability to the disease. So far, genome-wide association studies (GWAS) and candidate gene studies have established many OA-related loci. However, these findings account for only a rather small fraction of the genetic component. To further reveal the genetic architecture of OA, we conducted this case-control study to explore the association of locus EN1 rs4144782 and knee OA susceptibility in a Chinese population. EN1 rs4144782 was significantly associated with increased risk of knee OA (OR=1.26; 95% CI: 1.05-1.50, P value=0.012). In dominant model, compared with carriers of GG genotype, those with AG or AA genotype have an 1.44-fold increased risk of OA (OR: 1.44; 95% CI: 1.10-1.88; P value=0.008). Subgroup analyses didn't change the results materially. This should be the first association study of EN1 locus on risk of OA, and our finding suggested that the EN1 rs4144782 might contribute to the susceptibility of knee OA.

Citing Articles

Genome-Wide Differentially Methylated Region Analysis to Reveal Epigenetic Differences of Articular Cartilage in Kashin-Beck Disease and Osteoarthritis.

Fan Y, Gao D, Zhang Y, Zhu J, Zhang F, Wang L Front Cell Dev Biol. 2021; 9:636291.

PMID: 33732704 PMC: 7957013. DOI: 10.3389/fcell.2021.636291.

The Methylation Pattern for Knee and Hip Osteoarthritis.

Wu Z, Shou L, Wang J, Huang T, Xu X Front Cell Dev Biol. 2020; 8:602024.

PMID: 33240895 PMC: 7677303. DOI: 10.3389/fcell.2020.602024.

Analysis of methylation datasets identified significantly changed genes and functional pathways in osteoarthritis.

Han B, Zheng Z, Ren J, Qiu W, Li X Clin Rheumatol. 2019; 38(12):3529-3538.

PMID: 31376087 DOI: 10.1007/s10067-019-04700-4.

Osteoarthritis year in review 2018: genetics and epigenetics.

Jeffries M Osteoarthritis Cartilage. 2019; 27(3):371-377.

PMID: 30808485 PMC: 6292677. DOI: 10.1016/j.joca.2018.10.004.

References

Yamada Y . Association of a Leu(10)-->Pro polymorphism of the transforming growth factor-beta1 with genetic susceptibility to osteoporosis and spinal osteoarthritis. Mech Ageing Dev. 2000; 116(2-3):113-23. DOI: 10.1016/s0047-6374(00)00131-7. View

Kellgren J, Lawrence J . Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957; 16(4):494-502. PMC: 1006995. DOI: 10.1136/ard.16.4.494. View

Hamerman D, Stanley E . Implications of increased bone density in osteoarthritis. J Bone Miner Res. 1996; 11(9):1205-8. DOI: 10.1002/jbmr.5650110903. View

Etokebe G, Jotanovic Z, Mihelic R, Mulac-Jericevic B, Nikolic T, Balen S . Susceptibility to large-joint osteoarthritis (hip and knee) is associated with BAG6 rs3117582 SNP and the VNTR polymorphism in the second exon of the FAM46A gene on chromosome 6. J Orthop Res. 2014; 33(1):56-62. DOI: 10.1002/jor.22738. View

Syddall C, Reynard L, Young D, Loughlin J . The identification of trans-acting factors that regulate the expression of GDF5 via the osteoarthritis susceptibility SNP rs143383. PLoS Genet. 2013; 9(6):e1003557. PMC: 3694828. DOI: 10.1371/journal.pgen.1003557. View

Vaes R, Rivadeneira F, Kerkhof J, Hofman A, Pols H, Uitterlinden A . Genetic variation in the GDF5 region is associated with osteoarthritis, height, hip axis length and fracture risk: the Rotterdam study. Ann Rheum Dis. 2008; 68(11):1754-60. DOI: 10.1136/ard.2008.099655. View

Keen R, Hart D, Lanchbury J, Spector T . Association of early osteoarthritis of the knee with a Taq I polymorphism of the vitamin D receptor gene. Arthritis Rheum. 1997; 40(8):1444-9. DOI: 10.1002/art.1780400812. View

van der Steen S, Riedijk S, Verhagen-Visser J, Govaerts L, Srebniak M, Van Opstal D . The Psychological Impact of Prenatal Diagnosis and Disclosure of Susceptibility Loci: First Impressions of Parents' Experiences. J Genet Couns. 2016; 25(6):1227-1234. PMC: 5114319. DOI: 10.1007/s10897-016-9960-y. View

Webb B, Sullivan P, Skelly T, van den Oord E . Model-based gene selection shows engrailed 1 is associated with antipsychotic response. Pharmacogenet Genomics. 2008; 18(9):751-9. DOI: 10.1097/FPC.0b013e32830162bc. View

10.

Inanir A, Yigit S, Tural S, Cecen O, Yildirim E . MTHFR gene C677T mutation and ACE gene I/D polymorphism in Turkish patients with osteoarthritis. Dis Markers. 2012; 34(1):17-22. PMC: 3809745. DOI: 10.3233/DMA-2012-00939. View

11.

Lawrence P, Johnston P . On the role of the engrailed+ gene in the internal organs of Drosophila. EMBO J. 1984; 3(12):2839-44. PMC: 557774. DOI: 10.1002/j.1460-2075.1984.tb02217.x. View

12.

Evangelou E, Kerkhof H, Styrkarsdottir U, Ntzani E, Bos S, Esko T . A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip. Ann Rheum Dis. 2013; 73(12):2130-6. PMC: 4251181. DOI: 10.1136/annrheumdis-2012-203114. View

13.

Liu J, Cai W, Zhang H, He C, Deng L . Rs143383 in the growth differentiation factor 5 (GDF5) gene significantly associated with osteoarthritis (OA)-a comprehensive meta-analysis. Int J Med Sci. 2013; 10(3):312-9. PMC: 3575627. DOI: 10.7150/ijms.5455. View

14.

Valdes A, Spector T, Doherty S, Wheeler M, Hart D, Doherty M . Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations. Ann Rheum Dis. 2008; 68(12):1916-20. DOI: 10.1136/ard.2008.102236. View

15.

Evans D, Cailotto F, Parimi N, Valdes A, Castano-Betancourt M, Liu Y . Genome-wide association and functional studies identify a role for IGFBP3 in hip osteoarthritis. Ann Rheum Dis. 2014; 74(10):1861-7. PMC: 4449305. DOI: 10.1136/annrheumdis-2013-205020. View

16.

Yang P, Lung F, Jong Y, Hsieh H, Liang C, Juo S . Association of the homeobox transcription factor gene ENGRAILED 2 with autistic disorder in Chinese children. Neuropsychobiology. 2008; 57(1-2):3-8. DOI: 10.1159/000123115. View

17.

Joyner A, Martin G . En-1 and En-2, two mouse genes with sequence homology to the Drosophila engrailed gene: expression during embryogenesis. Genes Dev. 1987; 1(1):29-38. DOI: 10.1101/gad.1.1.29. View

18.

Martel-Pelletier J, Barr A, Cicuttini F, Conaghan P, Cooper C, Goldring M . Osteoarthritis. Nat Rev Dis Primers. 2016; 2:16072. DOI: 10.1038/nrdp.2016.72. View

19.

Shin M, Lee S, Kee S, Song S, Kweon S, Park D . Genetic association analysis of GDF5 and ADAM12 for knee osteoarthritis. Joint Bone Spine. 2012; 79(5):488-91. DOI: 10.1016/j.jbspin.2011.10.016. View

20.

Reynard L, Bui C, Syddall C, Loughlin J . CpG methylation regulates allelic expression of GDF5 by modulating binding of SP1 and SP3 repressor proteins to the osteoarthritis susceptibility SNP rs143383. Hum Genet. 2014; 133(8):1059-73. PMC: 4099533. DOI: 10.1007/s00439-014-1447-z. View