MicroRNA-15 suppresses viability, migration and invasion of the human MG-63 osteosarcoma cells via inhibition of cyclin dependent kinase 6 (CDK6).

MicroRNA-15a-3p (miR-15) acts as tumor-suppressor in different human cancers including osteosarcoma. Nonetheless, the molecular function of miR-15 in osteosarcoma via suppression of cyclin dependent kinase 6 (CDK6) is yet to be studied. The results showed significant downregulation of miR-15 in osteosarcoma tissues and cell lines. Overexpression of miR-15 inhibited the proliferation and colony formation of the MG-63 osteosarcoma cells via induction of apoptosis. Moreover, miR-15 inhibited the migration and invasion of MG-63 osteosarcoma cells. The tumor-suppressive functional role of miR-15 was shown to be exerted via suppression of CDK6. The expression of CDK6 was upregulated in osteosarcoma and its silencing could exert growth inhibitory effects on human osteosarcoma cells. However, overexpression of CDK6 could nullify the tumor-suppressive effects of miR-15 on the MG-63 osteosarcoma cells. Taken together, miR-15 negatively regulates growth, migration and invasion of osteosarcoma cells by targeting CDK6 at post-transcriptional level. These findings suggest the therapeutic potential of miR-15/CDK6 in human osteosarcoma.

The Ameliorative Effect of Mahuang Fuzi and Shenzhuo Decoction on Membranous Nephropathy of Rodent Model is Associated With Autophagy and Wnt/ß-Catenin Pathway.

The increased incidence of membranous nephropathy (MN) has made it the most common pathological type of primary nephrotic syndrome in adults in China. According to the theory of Traditional Chinese Medicine (TCM), Mahuang Fuzi (Chinese ephedra and Radix Aconiti Lateralis Preparata) and Shenzhuo Decoction (MFSD) could be used to treat such diseases. We treated patients of MN with MFSD, and observed comparable efficacy to glucocorticoid and/or immunosuppressants. In this study, we observed the therapeutic effect of MFSD on the rat model of passive Heymann nephritis (PHN), a classical MN model. Our results showed that MFSD treatment significantly reduced urinary protein level and podocyte injury in PHN rats, and correspondingly improved renal pathology, with the improvement effect on MN comparable to that of Cyclosporine A (CsA) alone. To explore the potential therapeutical mechanism of MFSD, the main chemical components of MFSD were determined by High-performance liquid chromatography-mass spectrometry (HPLC-MS). There were about 30 active components of MFSD. Next, based on network pharmacology methods, we screened related targets of MSFD on MN, which provided a preliminary understanding of the MFSD bioactive compounds. The clustering analysis showed that its active site might be in the autophagy-related protein and Wnt/ß-catenin pathway, which was related to podocyte injury. Finally, we observed an improvement in renal autophagy and a down-regulation of the Wnt/ß-catenin pathway after MSFD treatment in a PHN rat model. According to this study, autophagy and Wnt/ß-catenin pathway may be potential targets for MFSD in the treatment of MN.

Helper T Cells in Idiopathic Membranous Nephropathy.

Idiopathic membranous nephropathy (IMN) is an autoimmune disease in which the immune system produces an antibody response to its own antigens due to impaired immune tolerance. Although antibodies are derived from plasma cells differentiated by B cells, the T-B cells also contribute a lot to the immune system. In particular, the subsets of helper T (Th) cells, including the dominant subsets such as Th2, Th17, and follicular helper T (Tfh) cells and the inferior subsets such as regulatory T (Treg) cells, shape the immune imbalance of IMN and promote the incidence and development of autoimmune responses. After reviewing the physiological knowledge of various subpopulations of Th cells and combining the existing studies on Th cells in IMN, the role model of Th cells in IMN was explained in this review. Finally, the existing clinical treatment regimens for IMN were reviewed, and the importance of the therapy for Th cells was highlighted.

Mechanism of herbal medicine on hypertensive nephropathy (Review).

Hypertensive nephropathy is the most common complication of hypertension, and is one of the main causes of end­stage renal disease (ESRD) in numerous countries. The basic pathological feature of hypertensive nephropathy is arteriolosclerosis followed by renal parenchymal damage. The etiology of this disease is complex, and its pathogenesis is mainly associated with renal hemodynamic changes and vascular remodeling. Despite the increased knowledge on the pathogenesis of hypertensive nephropathy, the current clinical treatment methods are still not effective in preventing the development of the disease to ESRD. Herbal medicine, which is used to relieve symptoms, can improve hypertensive nephropathy through multiple targets. Since there are few clinical studies on the treatment of hypertensive nephropathy with herbal medicine, this article aims to review the progress on the basic research on the treatment of hypertensive nephropathy with herbal medicine, including regulation of the renin angiotensin system, inhibition of sympathetic excitation, antioxidant stress and anti­inflammatory protection of endothelial cells, and improvement of obesity­associated factors. Herbal medicine with different components plays a synergistic and multi­target role in the treatment of hypertensive nephropathy. The description of the mechanism of herbal medicine in the treatment of hypertensive nephropathy will contribute towards the progress of modern medicine.

The Potential Role of Regulatory B Cells in Idiopathic Membranous Nephropathy.

Regulatory B cells (Breg) are widely regarded as immunomodulatory cells which play an immunosuppressive role. Breg inhibits pathological autoimmune response by secreting interleukin-10 (IL-10), transforming growth factor-ß (TGF-ß), and adenosine and through other ways to prevent T cells and other immune cells from expanding. Recent studies have shown that different inflammatory environments induce different types of Breg cells, and these different Breg cells have different functions. For example, Br1 cells can secrete IgG4 to block autoantigens. Idiopathic membranous nephropathy (IMN) is an autoimmune disease in which the humoral immune response is dominant and the cellular immune response is impaired. However, only a handful of studies have been done on the role of Bregs in this regard. In this review, we provide a brief overview of the types and functions of Breg found in human body, as well as the abnormal pathological and immunological phenomena in IMN, and propose the hypothesis that Breg is activated in IMN patients and the proportion of Br1 can be increased. Our review aims at highlighting the correlation between Breg and IMN and proposes potential mechanisms, which can provide a new direction for the discovery of the pathogenesis of IMN, thus providing a new strategy for the prevention and early treatment of IMN.

MMP20 Single-Nucleotide Polymorphisms Correlate with Susceptibility to Alcohol-Induced Osteonecrosis of the Femoral Head in Chinese Males.

BACKGROUND Alcohol-induced osteonecrosis of the femoral head (ONFH) is caused by the interaction of genetic and environmental factors. Genetic variations of matrix metalloproteinase (MMP) system are associated with ONFH development and progression. In this study, we aimed to evaluate the relationships between MMP20 gene polymorphisms and the risk of alcohol-induced ONFH in Chinese Han males. MATERIAL AND METHODS In this case-control study, genotypes of 14 selected SNPs in the MMP20 gene were assayed using MassARRAY in 299 male cases with alcohol-induced ONFH and in 197 healthy males. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the influence of gene polymorphism on occurrence of alcohol-induced ONFH by allelic model analysis, genotype model analysis and haplotype analysis. RESULTS After allelic model analysis, the minimum alleles of rs10895322, rs1784424, rs3781788, and rs1573954 correlated with an increased risk of alcohol-induced ONFH (P<0.05). Genetic model analysis revealed significant associations of 9 SNPs with alcohol-induced ONFH occurrence even after adjustment for age (P<0.05): 2 protective SNPs (rs1711423 and rs1784418) and 7 high-risk SNPs (rs10895322, rs1784424, rs3781788, rs7126560, rs1573954, rs1711399, and rs2292730). Moreover, 8 SNPs showed a statistically significant association with different clinical phenotypes (P<0.05). Beyond that, haplotype "CGGTTCCA" in MMP20 was discovered to correlate with a 1.63-fold increased risk of alcohol-induced ONFH (OR: 1.63, 95% CI: 1.15-2.30, P=0.0058). CONCLUSIONS Our data sheds new light on the associations of MMP20 gene polymorphisms with alcohol-induced ONFH predisposition in Chinese Han males.

Correction: MMP-3 gene polymorphisms are associated with increased risk of osteoarthritis in Chinese men.

[This corrects the article DOI: 10.18632/oncotarget.18493.].

MMP-3 gene polymorphisms are associated with increased risk of osteoarthritis in Chinese men.

Osteoarthritis (OA) is the most common late-onset degenerative joint disease., It is characterized by progressive degradation of articular cartilage. We investigated the association between OA occurrence and single nucleotide polymorphisms (SNPs) in the matrix metalloproteinase-3 (MMP-3) gene involved in the breakdown of extra-cellular matrix proteins. The study included 100 male OA patients and 197 healthy men from the north area of China. Eight MMP-3 SNPs were genotyped. Odds ratios (ORs) with 95% confidence intervals (95%CIs) and multivariate logistic regression analysis were used to assess the association. Multivariate logistic regression analysis was used to identify SNPs that correlated with OA susceptibility. We found that rs639752 (dominant, OR = 2.03, 95% CI: 1.03-4.01, P = 0.038; over-dominant, OR = 2.00, 95% CI: 1.03-3.88, P = 0.037); rs520540 (dominant, OR = 2.03, 95% CI: 1.03-4.01, P = 0.038; over-dominant, OR = 2.00, 95% CI: 1.03-3.88, P = 0.037); rs602128 (dominant, OR = 2.03, 95% CI: 1.03-4.01, P = 0.038; over-dominant, OR = 2.01, 95% CI: 1.03-3.89, P = 0.037); and rs679620 (dominant, OR = 2.03, 95% CI: 1.03-4.01, P = 0.038; over-dominant, OR = 2.04, 95% CI: 1.05-3.96, P = 0.033) were associated with the increased risk of OA. Our results suggest that these SNPs may contribute to OA development, and could serve as molecular markers of OA susceptibility.

MMP9 polymorphism is associated with susceptibility to non-traumatic osteonecrosis of femoral head in a Chinese Han population.

Non-traumatic osteonecrosis of femoral head (ONFH) is an orthopedic refractory disease with escalating morbidity in Chinese Han population. In our case-control study, we examined eight previously identified MMP9 single-nucleotide polymorphisms (SNPs) in 585 non-traumatic ONFH patients and 507 healthy individuals from northern China to determine whether these SNPs associated with the risk of developing non-traumatic ONFH. Genetic model and haplotype analyses were used to evaluate the association between SNPs and non-traumatic ONFH. MMP9 rs2274755 (OR, 0.740; 95% CI, 0.578-0.949; p = 0.017) was associated with a reduced risk of non-traumatic ONFH. After adjusting for age and gender, the logistic regression results showed that rs2274755 associated with a lower risk of non-traumatic ONFH in the dominant (OR=0.71, 95% CI: 0.54-0.94, p=0.016), overdominant (OR=0.73, 95% CI: 0.55-0.96, p=0.026) and log-additive (OR=0.74740; 95% CI, 0.578-0.949; p=0.017) models. In addition, the "TGC" haplotype of rs2274755 was associated with a 0.79-fold decrease in risk while the "CTC" haplotype associated with a 0.65-fold decrease risk of the non-traumatic ONFH. These results provide evidence that the MMP9 SNP at the rs2274755 locus is associated with a decreased risk of non-traumatic ONFH in a Chinese Han population.

Association between alcohol-induced osteonecrosis of femoral head and risk variants of MMPS in Han population based on a case-control study.

The study aimed to evaluate the association between MMP gene superfamily and alcohol-induced osteonecrosis of femoral head (alcohol-induced ONFH) risk given its high prevalence, poor therapeutic effect, and serious clinical prognosis. 308 subjects (mean age, 49.47 years; males, 64.0%) who participated in our control group and 300 alcohol-induced ONFH patients (mean age, 43.29 years; males, 99.7%) formed the case group was enrolled to estimate by statistical analysis. We selected 23 single nucleotide polymorphisms (SNPs) from MMPs, and performed the chi-squared test, Fisher's exact test, t-test and genetic model analyses. From the result, rs243849 which located in MMP2 were 1.355 (1.014-1.811), 1.34 (1.01-1.78) in allele model and log-addictive model, respectively. And the p-value of rs243849 in Cochran-Armitage trend test is 0.044. Unfortunately, the similar results of these SNPs were not observed when adjusted by gender and age. Our study is not enough to supply a positive result to benefit for alcohol-induced ONFH clinical prevention, but guide out a new direction for further experiment.

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

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.

MMP8 polymorphism is associated with susceptibility to osteonecrosis of the femoral head in a Chinese Han population.

Osteonecrosis of the femoral head (ONFH) is an orthopedic refractory disease that adversely affects quality of life. Matrix metalloproteinase-8 (MMP-8) produced by the bone marrow has been implicated in the degradation of collagen during bone development. We assessed whether MMP8 polymorphisms are associated with ONFH. In a case-control study, using χ2 tests and genetic model analyses, we genotyped 5 MMP8 single-nucleotide polymorphisms (SNPs) in 585 ONFH patients and 507 healthy control subjects in a Chinese Han population. The MMP8 rs11225394 SNP was associated with an increased risk of ONFH in an allele model (OR=1.34; 95% CI, 1.003-1.786, P=0.047). In addition, rs11225394 was associated with an increased risk of ONFH in a dominant model (OR =1.39, 95% CI, 1.02-1.89, P=0.036), over-dominant model (OR=1.39, 95% CI, 1.02-1.89, P=0.038), and log-additive model (OR =1.36, 95% CI, 1.01-1.84, P=0.039). After adjusting for age and gender, rs11225394 was associated with ONFH in a dominant (OR =1.44, 95% CI, 1.05-1.96, P=0.023), over-dominant (OR =1.44, 95% CI, 1.05-1.98, P=0.022), and log-additive model (OR =1.40, 95% CI, 1.04-1.90, P=0.027). These results provide the first evidence that MMP8 SNP at the rs11225394 locus is associated with the increased risk of ONFH in Chinese Han population.

Association between genetic polymorphism of telomere-associated gene ACYP2 and the risk of HAPE among the Chinese Han population: A Case-control study.

High-altitude pulmonary edema (HAPE) is a hypoxia-induced, life-threatening, pulmonary edema, which is characterized by exaggerated pulmonary hypertension caused by stress failure. ACYP2 was found to associated with telomere length, the aim of this study was to identify whether ACYP2 polymorphisms increase or decrease HAPE risk in the Chinese Han individuals.In present study, we have genotyped 7 single-nucleotide polymorphisms (SNPs) in ACYP2 to determine the haplotypes in a case-control study with 265 HAPE patients and 303 healthy individuals. Genotypes were determined using the Sequenom MassARRAY method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression with adjustment for gender and age. We found 3 SNPs yielded significant evidence for association with HAPE risk which had not been investigated before. Rs6713088 was found to have a 1.85- and 1.30-fold increased risk of HAPE in the recessive and additive model. The GT of rs843752 also conferred an increased risk of HAPE (GT/TT: OR = 1.51, 95% CI: 1.05-2.16, P = 0.026) and the genotype frequency distributions of rs843752 had significant difference between cases and controls. The CC genotype of rs17045754 had a protect effect on HAPE patients, and it was found to have a 0.29-fold reduced risk of HAPE in the recessive model.Although additional, larger population-based studies are needed to confirm these findings, our study shed light on the association between ACYP2 variant and HAPE risk in Han Chinese population for the first time.

TIMP-2 SNPs rs7342880 and rs4789936 are linked to risk of knee osteoarthritis in the Chinese Han Population.

This study aimed to investigate whether functional polymorphisms in the tissue inhibitors of metalloproteinase-2 (TIMP-2) gene are associated with susceptibility to knee osteoarthritis (OA) in the Chinese Han population. Six TIMP-2 single nucleotide polymorphisms (SNPs) were assayed using MassARRAY in 300 patients clinically and radiographically diagnosed with knee OA and in 428 controls. Allelic and genotypic frequencies were compared between groups. Logistic regression adjusting for age and gender was used to estimate risk associations between specific genotypes and knee OA by computing odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that allele "A" in rs7342880 was significantly associated with increased risk of knee OA (OR = 1.44, 95%CI = 1.09-1.91, p = 0.035). In addition, in the over-dominant model, rs4789936 correlated with reduced risk of knee OA, adjusting for age and gender (OR = 0.69, 95%CI = 0.49-0.98, p = 0.036). Finally, rs7342880 correlated with increased risk of knee OA in females. This study provides evidence that TIMP-2 is a knee OA susceptibility gene in the Chinese population and a potential diagnostic and preventive marker for the disease.

Association analysis of ANK3 gene variants with schizophrenia in a northern Chinese Han population.

Schizophrenia is a chronic, severely debilitating mental disorder. Many studies have suggested that genetic factors play an important role in the onset and development of schizophrenia. In our study, we conducted a case-control study in a northern Chinese Han population of 499 schizophrenia patients and 500 controls to investigate the effect of variant genotypes of 13 SNPs in ANK3 on schizophrenia risk. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the chi-squared test, genetic model analysis, and haplotype analysis. Four ANK3 SNPs were associated with schizophrenia risk. The minor allele of rs958852 in ANK3 was associated with a 0.75-fold reduction in schizophrenia risk in an allelic model. In the genetic model, rs958852 was associated with a reduced schizophrenia risk, and rs10994336, rs10994338 and rs4948418 were associated with an increased schizophrenia risk (rs10994336, OR = 2.00, 95%CI: 1.01-3.94, p = 0.047; rs10994338, OR = 1.99, 95%CI: 1.01-3.93, p = 0.047; rs4948418, OR = 2.00, 95%CI: 1.01-3.94, p = 0.047). In addition, haplotype "TTC" of ANK3 was associated with a 0.73-fold reduced schizophrenia risk (95%CI: 0.54-0.99; p = 0.044). To our knowledge, this is the first to report of an association between ANK3 rs10994336, rs10994338, rs4948418 and rs958852 and schizophrenia risk in a northern Chinese Han population.

IL-10 and PRKDC polymorphisms are associated with glioma patient survival.

Interleukin-10 (IL-10) and DNA repair gene PRKDC mutations are implicated in the development of multiple human cancers, including glioma. We investigated associations between IL-10 and PRKDC gene polymorphisms and prognosis in low- and high-grade glioma patients. We analyzed the associations of one IL-10 and one PRKDC single nucleotide polymorphism with patient clinical factors in 481 glioma patients using Cox proportional hazard models and Kaplan-Meier curves. We also assessed associations between patient clinical characteristics and prognosis. Our data showed that the extent of tumor resection (gross-total resection) and application of chemotherapy were associated with improved patient outcomes in all glioma cases. Additionally, univariate (Log-rank p = 0.019) and multivariate Cox regression analyses (p = 0.022) showed that the IL-10 rs1800871 C/T genotype correlates with improved overall survival in cases of low-grade glioma, whereas the PRKDC rs7003908 C/C genotype correlated with reduced overall and progression-free survival in high-grade glioma patients in univariate (Log-rank p = 0.000 and p = 0.000, respectively) and multivariate Cox regression analyses (p = 0.001; p = 0.002, respectively). These results suggest that IL-10 rs1800871 and PRKDC rs7003908 may be useful biomarkers for predicting glioma patient outcome. Further functional studies are needed to evaluate the mechanisms by which these polymorphisms affect glioma progression.

Association between genetic polymorphisms of MMP8 and the risk of steroid-induced osteonecrosis of the femoral head in the population of northern China.

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (ONFH) is the most common clinical nontraumatic ONFH. Once ONFH occurs, it seriously reduces patients' quality of life. The matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) system was found to play a significant role in the development of ONFH. The aim of this study was to identify the associations between 7 genes selected from the MMP/TIMP system and steroid-induced ONFH. METHODS: We genotyped 34 single-nucleotide polymorphisms (SNPs) of 7 genes selected from the MMP/TIMP system in a case-control study with 285 cases of steroid-induced ONFH and 308 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi-squared test, genetic model analysis, haplotype analysis, and stratification analysis. RESULTS: We found that the minor alleles of rs1940475 and rs11225395 in MMP8 were associated with a 1.32-fold increased risk of steroid-induced ONFH in the allelic model analysis (P = 0.021 and 0.022, respectively). In the genetic model analysis, we found that rs3740938, rs2012390, rs1940475, and rs11225395 were associated with an increased risk of steroid-induced ONFH. In further stratification analysis, rs3740938 and rs2012390 displayed a significantly increased risk of steroid-induced ONFH in females under the dominant (rs3740938, OR = 2.69, 95% CI: 1.50-4.83, P = 0.001; rs2012390, OR = 2.30, 95% CI: 1.31-4.03, P = 0.012) and additive (rs3740938, OR = 2.02, 95% CI: 1.24-3.29, P = 0.010; rs2012390, OR = 1.77, 95% CI: 1.12-2.80, P = 0.047) models. In addition, haplotype "AGTCA" of MMP8 was found to be associated with a 1.40-fold increased risk of steroid-induced ONFH (95% CI: 1.04-1.88, P = 0.025). CONCLUSION: Our results verify that genetic variants of MMP8 contribute to steroid-induced ONFH susceptibility in the population of northern China. In addition, we found that gender differences might interact with MMP8 polymorphisms to contribute to the overall susceptibility to steroid-induced ONFH.

A single-nucleotide polymorphism in MMP9 is associated with decreased risk of steroid-induced osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is a common hip joint disease, and steroid-induced ONFH accounts for a large number of cases. Here, we examined eight previously-identified single-nucleotide polymorphisms (SNPs) in the MPP2 and MPP9 genes of 285 steroid-induced ONFH patients and 507 healthy controls from northern China to determine whether these SNPs were associated with the risk of developing steroid-induced ONFH. Chi-squared tests and genetic model and haplotype analyses were used to evaluate associations. The rs2274755 SNP in MMP9 was associated with a decreased risk of steroid-induced ONFH in the allele, dominant, and additive models. Additionally, the "CGC" MMP9 haplotype was associated with a 0.69-fold decrease in the risk of steroid-induced ONFH. Although additional, larger population-based studies are needed to confirm these findings, our results reveal for the first time an association between a MMP9 SNP at the rs2274755 locus and a decreased risk of steroid-induced ONFH in a northern Chinese population.

Telomere length-related gene ACYP2 polymorphism is associated with the risk of HAPE in Chinese Han population.

BACKGROUND: High altitude pulmonary edema (HAPE) is a type of pneumonedema that mostly occurs under conditions such as high altitude, rapid ascent and hypoxia, amongst others. The ACYP2 polymorphism is suggested to be associated with mean telomere length, and telomere length is significantly longer at a moderate attitude than at sea-level or at simulated high attitude. The present study aimed to determine whethher there is any association between ACYP2 polymorphism and the risk of HAPE. METHODS: A total of 265 patients and 303 healthy controls were enrolled in our case-control study. Six SNPs were selected and genotyped using the Sequenom MassARRAY method. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression with adjustment for gender and age. RESULTS: Using chi-squared tests, we found that the minor allele G of rs11896604 is significantly associated with a decreased risk of HAPE [odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.65-1.16, p = 0.048]. We also found that the 'A/A' genotype of rs12615793 is associated with a decreased risk of HAPE based on the recessive model (OR =0.28; 95% CI = 0.09-0.88; p = 0.017). Additionally, the 'G/G' genotype of rs11896604 was found to be associated with a decreased risk of HAPE based on the codominant model (OR =0.26; 95% CI = 0.08-0.79; p = 0.025) and recessive model (OR =0.25; 95% CI = 0.08-0.77; p = 0.007). However, only rs11896604 remained significant after Bonferroni correction (p < 0.0083). CONCLUSIONS: The present study found that the ACYP2 gene polymorphism significantly decreased the risk of HAPE. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.