Polymorphic variation of hypoxia inducible factor-1 A (HIF1A) gene might contribute to the development of knee osteoarthritis: a pilot study

Abstract

BackgroundOsteoarthritis (OA) is a multifactorial degenerative condition of the whole joint with a complex pathogenesis whose development and progression is significantly mediated by interactions between the joint cartilage and articular tissues, particularly, proinflammatory mediators and oxidative stress, which results in cartilage deterioration and subchondral bone destruction. HIF-1 alpha regulates oxygen homeostasis in hypoxic tissues such as joint cartilage; efficiency of transcriptional activity of the HIF1A gene is strongly influenced by the presence of polymorphic variants. Given the loss of articular cartilage and with intention to restore damaged tissue, WISP-1 participates in the development of subchondral bone; further, its expression is highly increased in chondrocytes of OA patients. The aim of this study was to evaluate gene frequencies of HIF1A and WISP1 polymorphisms in Mexican patients suffering from knee OA.MethodsWe determined HIF1A rs11549465 (P582S), rs11549467 (A588T), and rs2057482 (C191T), and WISP1 rs2929970 (A2364G) polymorphisms in 70 Mexican patients with knee OA and compare them to those present in 66 ethnically matched healthy controls. Genotyping for these polymorphisms was performed by Real-Time PCR using TaqMan probes.ResultsGene frequencies exhibited a significant increase of the CC genotype of rs11549465 polymorphism in knee OA patients as compared with those present in controls (P = 0.003 OR = 5.7, 95 % CI = 1.7–21.6); CT genotype and T allele showed decreased frequency in the knee OA group vs. the controls (P = 0.003 OR = 0.2, CI = 0.05–0.6; and P = 0.004 OR = 0.2, CI = 0.05–0.65, respectively). Allele frequencies of the other polymorphic variants were similar in both patients and controls.ConclusionsThese results suggest that the presence of the rs11549465 SNP (HIF1A) plays a role protective in the loss of articular cartilage in our population, and offers the possibility to further study the molecular mechanisms within cartilage and subchondral bone.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-015-0678-z) contains supplementary material, which is available to authorized users.

Effect of genetic variation in microRNA binding site in WNT1-inducible signaling pathway protein 1 gene on oral squamous cell carcinoma susceptibility

“…However, the WISP1 SNPs contributing to cancer progression have yet to be extensively investigated. In the present study, we found that the WISP1 SNP of rs2929970 was associated with OSCC risk (Table 2); rs2929970 is located in the 3′ untranslated region within a region of splicing variation [38]. Our present study confirmed the association of the clinically examined rs2929970 in the WISP1 3′-UTR region with OSCC risk; this association is most likely attributed to a putative hsa-miRNA-99a binding site (Fig 1).…”

Phagocytosis of monosodium urate crystals by human synoviocytes induces inflammation

“…9,10 In normoxic conditions, HIF-1a is hydroxylated on proline residues and allows recognition by the von Hippel-Lindau protein (pVHL) that targets HIF-a for proteasomal degradation. 11 However, during hypoxia, HIF-1a hydroxylation is inhibited and accumulates in the cytoplasm with subsequent translocation into nucleus and promote the gene expression hypoxia-sensitive like NOS2, VEGF, SOX9, COL2A1, among others, involved in various cellular and systemic adaptive responses to hypoxia, including angiogenesis, vasomotor regulation, cell proliferation and survival, cell death, and extracellular matrix metabolism. 11,12 Additionally, HIF-1a is inducible by cytokines, including the hepatocyte growth factor (HGF), a cytokine produced from stromal cells that functions as a mitogen, morphogen.…”

“…11 However, during hypoxia, HIF-1a hydroxylation is inhibited and accumulates in the cytoplasm with subsequent translocation into nucleus and promote the gene expression hypoxia-sensitive like NOS2, VEGF, SOX9, COL2A1, among others, involved in various cellular and systemic adaptive responses to hypoxia, including angiogenesis, vasomotor regulation, cell proliferation and survival, cell death, and extracellular matrix metabolism. 11,12 Additionally, HIF-1a is inducible by cytokines, including the hepatocyte growth factor (HGF), a cytokine produced from stromal cells that functions as a mitogen, morphogen. 13,14 Also, HGF exhibits strong angiogenic properties through its ability to induce the expression of vascular endothelial growth factor (VEGF), which is another potent inflammatory and angiogenic factor and a classical mediator of sensitization of unmyelinated sensory nerves.…”

HIF1A gene polymorphisms and human diseases: Graphical review of 97 association studies

“…Among 16 HIF1A SNPs associated with 40 different phenotypes six SNPs have been associated with increased risk for 14 cancer types: rs113182457, rs11549465, rs11549467, rs199775054, rs2057482, and rs2301113 . These six SNPs were most frequently associated with breast, lung, colorectal (CRC), gastric, prostate, oral cancer, and renal cell carcinoma (RCC).…”