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

ABSTRACT: BACKGROUND:Osteoarthritis (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. METHODS:We 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. RESULTS:Gene 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. CONCLUSIONS:These 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.

SUBMITTER: Fernandez-Torres J

PROVIDER: S-EPMC4546180 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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

Fernández-Torres Javier J Hernández-Díaz Cristina C Espinosa-Morales Rolando R Camacho-Galindo Javier J Galindo-Sevilla Norma del Carmen Ndel C López-Macay Ámbar Á Zamudio-Cuevas Yessica Y Martínez-Flores Karina K Santamaría-Olmedo Mónica Guadalupe MG Pineda Carlos C Granados Julio J Martínez-Nava Gabriela Angélica GA Gutiérrez Marwin M López-Reyes Alberto G AG

BMC musculoskeletal disorders 20150821

<h4>Background</h4>Osteoarthritis (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 transcri ...[more]

PMID: 26293784

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Project description:BACKGROUND:Hypoxia inducible factor 1-alpha (HIF1A) is a transcription factor that plays important role in regulating cascade of reactions. In this study, the effect of rs11549465 (1772 C/T) and rs11549467 (1790 G/A) polymorphisms of HIF1A gene and its association with cancers were investigated through meta-analysis. METHODS:Meta-analysis of genome wide association studies of HIF1A 1772 C/T polymorphism were conducted on 22 case-control studies of sample size 19024 and for 1790 G/A polymorphism 19 case-control studies were included with sample size 10654. Genotype and allelic frequency compared between cases and controls together with further subgroup analyses were carried out by cancer type and ethnicity. RESULTS:Meta-analysis from this study indicated that HIF1A 1772 C/T polymorphism is significantly associated with overall cancer risk. T allele and genotype TT are significantly associated with increasing overall cancer risk; odds ratios (OR) dominant model [TT?+?CT vs. CC: OR 1.30, 95 % CI (1.06-1.59), p-value: 0.0115], and T allele vs. C allele: OR 1.32, 95 % CI (1.07-1.63), p-value: 0.0098. Also, HIF1A 1790 G/A polymorphism, analyses showed that A allele and genotype AA are significantly associated with increasing overall cancer risk; odds ratios (OR) homozygote comparison [AA vs. GG: OR 5.10, 95 % CI (3.12-8.33), p-value: <0.0001], heterozygote comparison [GA vs. GG: OR 1.74, 95 % CI (1.20-2.52), p-value: 0.0033], dominant model [AA?+?GA vs. GG: OR 1.82, 95 % CI (1.26-2.62), p-value: 0.0014], recessive model [AA vs. GA?+?GG: OR 3.79, 95 % CI (2.34-6.15), p-value: <0.0001] and A allele vs. G allele: OR 1.82, 95 % CI (1.31-2.52), p-value: 0.0003. CONCLUSION:In detail meta-analysis indicated that both the polymorphisms 1772 C/T and 1790 G/A are significantly associated with overall cancer risk. The subgroup analyses showed that lung cancer is significantly associated with both polymorphisms. Although the 1772 C/T polymorphism is significantly associated with decreasing risk of renal cell carcinoma but the 1790 G/A polymorphism has shown to significantly increase the cancer risk in both Caucasian and Asian population. Thus, HIF1A could be a useful prognostic marker for cancers early predisposition.

Dataset Information

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

Publications

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

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