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      MMP-3 and MMP-8 single-nucleotide polymorphisms are related to alcohol-induced osteonecrosis of the femoral head in Chinese males

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          Abstract

          Our study investigated the association between MMP-3 and MMP-8 single-nucleotide polymorphisms (SNPs) and alcohol-induced osteonecrosis of the femoral head (ONFH) in 695 Chinese males (299 cases and 396 control subjects). The minor allele of MMP-3 rs650108 was associated with a 0.78-fold decrease in alcohol-induced ONFH risk in the allelic model (95% CI = 0.63-0.97, P = 0.026). In the genetic model adjusted for age, rs650108 was associated with decreased risk of alcohol-induced ONFH in the dominant model (OR = 0.68, 95% CI = 0.49-0.95, P = 0.022) and log-additive model (OR = 0.78, 95% CI = 0.63-0.98, P = 0.030); MMP-8 rs11225394 was associated with increased risk in the codominant model (OR = 1.72, 95% CI = 1.15-2.58, P= 0.010), dominant model (OR = 1.67, 95% CI = 1.12-2.48, P = 0.012), over-dominant model (OR = 1.73, 95% CI = 1.16-2.59, P = 0.007) and log-additive model (OR = 1.57, 95% CI= 1.07-2.32, P = 0.022); and MMP-8 rs2012390 was associated with decreased risk in the dominant model (OR = 0.72, 95% CI = 0.53-0.97, P = 0.032) and log-additive model (OR = 0.77, 95% CI = 0.60-0.98, P = 0.035). Haplotype analysis showed that the CGATATGT sequence mediated decreased alcohol-induced ONFH risk (OR = 0.75, 95% CI = 0.57-0.97, P = 0.029). Therefore, among Chinese males, MMP-3 rs650108 and MMP-8 rs2012390 decrease alcohol-induced ONFH risk and MMP-8 rs11225394 increases it. Further study is needed to validate our conclusion.

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          High-throughput oncogene mutation profiling in human cancer.

          Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention.
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            Statistics notes. The odds ratio.

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              Nontraumatic osteonecrosis of the femoral head: ten years later.

              The etiology of osteonecrosis of the hip may have a genetic basis. The interaction between certain risk factors and a genetic predisposition may determine whether this disease will develop in a particular individual. The rationale for use of joint-sparing procedures in the treatment of this disease is based on radiographic measurements and findings with other imaging modalities. Early diagnosis and intervention prior to collapse of the femoral head is key to a successful outcome of joint-preserving procedures. The results of joint-preserving procedures are less satisfactory than the results of total hip arthroplasty for femoral heads that have already collapsed. New pharmacological measures as well as the use of growth and differentiation factors for the prevention and treatment of this disease may eventually alter our treatment approach, but it is necessary to await results of clinical research with long-term follow-up of these patients.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                11 April 2017
                21 February 2017
                : 8
                : 15
                : 25177-25188
                Affiliations
                1 Inner Mongolia Medical University, Hohhot, Inner Mongolia 010030, China
                2 Department of the 2nd Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010030, China
                3 Zhengzhou Traditional Chinese Medicine Traumatology Hospital, Zhengzhou, Henan 450016, China
                4 School of Life Sciences, Northwest University, Xi’an, Shaanxi 710069, China
                5 Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, China
                6 Key Laboratory of High Altitude Environment and Genes Related to Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, China
                7 Key Laboratory for Basic Life Science Research of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, China
                Author notes
                Correspondence to: Jianzhong Wang, wangjianzhongWJ@ 123456163.com
                Article
                15587
                10.18632/oncotarget.15587
                5421920
                28445942
                e25accaf-4007-4087-81af-bd42765bdff4
                Copyright: © 2017 Chen et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 8 September 2016
                : 27 January 2017
                Categories
                Research Paper

                Oncology & Radiotherapy
                mmp-3,mmp-8,alcohol-induced osteonecrosis of the femoral head,genetic,single-nucleotide polymorphism

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