Genetic association of angiogenesis- and hypoxia-related gene polymorphisms with osteonecrosis of the femoral head

Jung Min Hong; 김태호; Hyun-Ju Kim; 박의균; 김신윤; 양은경

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자료유형: 학술저널

저자정보: Jung Min Hong 김태호 Hyun-Ju Kim 박의균 김신윤 양은경

저널정보: 대한생화학·분자생물학회 Experimental and Molecular Medicine Experimental and Molecular Medicine 제42권 제5호

발행연도: 2010.1

수록면: 376 - 385 (10page)

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Multiple factors have been implicated in the development of osteonecrosis of the femoral head (ONFH). In particular, non-traumatic ONFH is directly or indirectly related to injury of the vascular supply to the femoral head. Thus, hypoxia in the femoral head caused by impaired blood flow may be an important risk factor for ONFH. In this study, we investigated whether genetic variations of angiogenesis- and hypoxia-related genes contribute to an increased risk for the development of ONFH. Candidate genes were selected based on known hypoxia and angiogenesis pathways. An association study was performed using an Affymetrix Targeted Genotyping 3K Chip array with 460 ONFH patients and 300 control subjects. We showed that single nucleotide polymorphisms (SNPs) in the genes TF,VEGFC, IGFBP3, and ACE were associated with an increased risk of ONFH. On the other hand, SNPs in the KDR and NRP1 genes were associated with protection against ONFH. The most important finding was that one SNP (rs2453839) in the IGFBP3 gene was significantly associated with a higher risk of ONFH (P =0.0061, OR 7.74). In subgroup analysis, most candidate gene variations that were associated with ONFH occurred in the idiopathic subgroup. Among other SNPs,ACE SNPs were associated with steroid-induced ONFH (P = 0.0018-0.0037, OR ＞ 3). Collectively, our findings suggest that genetic variations in angiogenesis-and hypoxia-related genes may help to identify susceptibility factors for the development of ONFH in the Korean population.

#anoxia #Asian continental ancestry group #femur head #neovascularization #physiologic #osteonecrosis #polymorphism #single nucleotide

참고문헌 (27)

참고문헌 신청

Arnett TR / 2003 / Hypoxia is a major stimulator of osteoclast formation and bone resorption / J Cell Physiol 19 : 2 ~ 8

Beckman LE / 1998 / DNA polymorphisms and haplotypes in the human transferrin gene / Hum Genet 102 : 141 ~ 44

Bjorkman A / 2004 / Factor V leiden and prothrombin gene mutation: risk factors for osteonecrosis of the femoral head in adults / Clin Orthop Relat Res : 168 ~ 172

Cao Y / 1998 / Vascular endothelial growth factor C induces angiogenesis in vivo / Proc Nat Acad Sci USA : 14389 ~ 14394

Carlevaro MF / 1997 / Transferrin promotes endothelial cell migration and invasion: implication in cartilage neovascularization / J Cell Biol 136 : 1375 ~ 1384

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