Search

The human sex ratio (fraction of males) at birth is close to 0.5 at the population level, an observation commonly explained by Fisher's principle. However, past human studies yielded conflicting results regarding the existence of sex ratio-influencing mutations—a prerequisite to Fisher's principle, raising the question of whether the nearly even population sex ratio is instead dictated by the random X/Y chromosome segregation in male meiosis. Here we show that, because a person's offspring sex ratio (OSR) has an enormous measurement error, a gigantic sample is required to detect OSR-influencing genetic variants. Conducting a UK Biobank-based genome-wide association study that is more powerful than previous studies, we detect an OSR-associated genetic variant, which awaits verification in independent samples. Given the abysmal precision in measuring OSR, it is unsurprising that the estimated heritability of OSR is effectively zero. We further show that OSR's estimated heritability would remain virtually zero even if OSR is as genetically variable as the highly heritable human standing height. These analyses, along with simulations of human sex ratio evolution under selection, demonstrate the compatibility of the observed genetic architecture of human OSR with Fisher's principle and render it plausible that multiple OSR-influencing genetic variants segregate among humans. [ABSTRACT FROM AUTHOR]

Abstract Background Current evidence of the association between a single nucleotide polymorphism (SNP) in ADAMTS14 (rs4747096) and osteoarthritis (OA) is controversial. This study aimed to determine whether the ADAMTS14 SNP is closely related to OA risk. Methods An electronic search of for the association between the rs4747096 polymorphisms and OA was performed using four online databases (updated on September 10, 2022). The association between susceptibility to OA and rs4747096 polymorphism was evaluated in four genetic models: the allele (mutation [A] vs. wild type [G]), additive (AA vs. GG and AG vs. GG), recessive (AA vs. AG + GG), and dominant (AA + AG vs. GG). This meta-analysis was performed in the R software, and effects were assessed using odds ratios (ORs) and 95% confidence intervals (CI). Results Four studies (707 cases in the case group and 859 cases in the control group) were included. The results of the meta-analysis showed that, except in the recessive genetic model, there was a significant correlation between OA risk and the rs4747096 polymorphism using the allele (OR [95% CI] = 1.48 [1.26–1.73], P

Background: Current evidence of the association between a single nucleotide polymorphism (SNP) in ADAMTS14 (rs4747096) and osteoarthritis (OA) is controversial. This study aimed to determine whether the ADAMTS14 SNP is closely related to OA risk. Methods: An electronic search of for the association between the rs4747096 polymorphisms and OA was performed using four online databases (updated on September 10, 2022). The association between susceptibility to OA and rs4747096 polymorphism was evaluated in four genetic models: the allele (mutation [A] vs. wild type [G]), additive (AA vs. GG and AG vs. GG), recessive (AA vs. AG + GG), and dominant (AA + AG vs. GG). This meta-analysis was performed in the R software, and effects were assessed using odds ratios (ORs) and 95% confidence intervals (CI). Results: Four studies (707 cases in the case group and 859 cases in the control group) were included. The results of the meta-analysis showed that, except in the recessive genetic model, there was a significant correlation between OA risk and the rs4747096 polymorphism using the allele (OR [95% CI] = 1.48 [1.26–1.73], P < 0.001), additive (AG vs. GG, OR [95% CI] = 2.56 [1.79–3.65], P < 0.001; AA vs. GG, OR [95% CI] = 2.81 [1.98–3.98], P < 0.001), and dominant (OR [95% CI)] = 1.72 [1.34–2.2], P < 0.001) genetic models. Conclusions: The ADAMTS14 rs4747096 polymorphism is associated with susceptibility to OA. [ABSTRACT FROM AUTHOR]

Abstract Background Primary osteoarthritis is considered one of the most common and the most studied musculoskeletal disorder. Nevertheless, the risk factors remain unclear. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 14 (ADAMTS14) gene is involved in the cleavage of amino-terminal propeptides from type II procollagen, a necessary step in the formation of collagen fibers. The abnormal metabolism of collagen fibers type II leads to a decreased mechanical strength of joint cartilage which is one of the most important contributing factors to joint osteoarthritis. We aimed at investigating the association between primary osteoarthritis and ADAMTS14 gene rs4747096 single nucleotide polymorphism in a sample of Egyptian patients and analyzing the relationship between this genetic polymorphism with the severity of osteoarthritis. Sixty-five Egyptian patients who fulfilled the American College of Rheumatology criteria for primary knee osteoarthritis were compared with thirty-one apparently healthy subjects. Genotyping was performed by TaqMan single nucleotide polymorphism genotyping assay. Results There was a statistically significantly higher frequency of AA genotype among osteoarthritis patients compared to the control group (P = 0.004). The number of affected hand joints was significantly higher among patients with ADAMTS14 AA genotype in comparison to patients with ADAMTS14 AG genotype (P = 0.002). In addition, AA genotype was associated with statistically significantly higher Kellgren-Lawrence radiological grades in the knee and hand joints (proximal interphalangeal and thumb interphalangeal joints) (P = 0.037, 0.003, and 0.030 respectively). Conclusion The study showed an association between the AA genotype of ADAMTS14 gene rs4747096 single nucleotide polymorphism with knee and hand osteoarthritis and osteoarthritis severity in these joints. The AA genotype of ADAMTS14 gene rs4747096 single nucleotide polymorphism could be implicated in the increased incidence of primary osteoarthritis development and elevated disease severity among the Egyptian population.

Background: Primary osteoarthritis is considered one of the most common and the most studied musculoskeletal disorder. Nevertheless, the risk factors remain unclear. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 14 (ADAMTS14) gene is involved in the cleavage of amino-terminal propeptides from type II procollagen, a necessary step in the formation of collagen fibers. The abnormal metabolism of collagen fibers type II leads to a decreased mechanical strength of joint cartilage which is one of the most important contributing factors to joint osteoarthritis. We aimed at investigating the association between primary osteoarthritis and ADAMTS14 gene rs4747096 single nucleotide polymorphism in a sample of Egyptian patients and analyzing the relationship between this genetic polymorphism with the severity of osteoarthritis. Sixty-five Egyptian patients who fulfilled the American College of Rheumatology criteria for primary knee osteoarthritis were compared with thirty-one apparently healthy subjects. Genotyping was performed by TaqMan single nucleotide polymorphism genotyping assay. Results: There was a statistically significantly higher frequency of AA genotype among osteoarthritis patients compared to the control group (P = 0.004). The number of affected hand joints was significantly higher among patients with ADAMTS14 AA genotype in comparison to patients with ADAMTS14 AG genotype (P = 0.002). In addition, AA genotype was associated with statistically significantly higher Kellgren-Lawrence radiological grades in the knee and hand joints (proximal interphalangeal and thumb interphalangeal joints) (P = 0.037, 0.003, and 0.030 respectively). Conclusion: The study showed an association between the AA genotype of ADAMTS14 gene rs4747096 single nucleotide polymorphism with knee and hand osteoarthritis and osteoarthritis severity in these joints. The AA genotype of ADAMTS14 gene rs4747096 single nucleotide polymorphism could be implicated in the increased incidence of primary osteoarthritis development and elevated disease severity among the Egyptian population. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a very common malignancy in the world, but the effect of therapies on advanced HCC has not improved for decades. The present study aimed to investigate the role of miR-30a in the tumorigenesis of HCC. Methods: The expression of miR-30a and ADAMTS14 in HCC tissues were determined. Luciferase reporter gene detection confirmed the correlation between miR-30a and ADAMTS14. Cell viability and apoptosis rate were examined using an MTT assay and flow cytometry. Cell migration and invasion ability were detected by a transwell assay. The protein expression of ADAMTS14, β-catenin, GSK-3β, and p-GSK-3β were determined using western blotting. Results: miR-30a was negatively correlated with the expression of ADAMTS14 in HCC tissues. Further research confirmed that ADAMTS14 is the direct target of miR-30a. In addition, the expression of ADAMTS14, cell viability and apoptosis were suppressed by miR-30a overexpression, while knockdown of miR-30a led to the opposite result. miR-30a also inhibits the phosphorylation of GSK-3β and β-catenin, without changing the total GSK-3β level. Conclusions: miR-30a acts as a tumor suppressor in the progression of HCC and can be used as a biomarker for early prediction and diagnosis. [ABSTRACT FROM AUTHOR]

Background: ADAMTS14 played a crucial role in the formation and development of various cancers. Currently, no associations had been revealed between ADAMTS14 and clear cell renal cell carcinoma (ccRCC). Hence, this study was designed to assess the prognostic values and immunological roles of ADAMTS14 in ccRCC and to reveal its potential mechanisms. Methods: ADAMTS14-related expression profiles and related clinical data were downloaded from The Cancer Genome Atlas (TCGA) dataset, validated by the ICGC dataset, qRT-PCR, and immunohistochemistry. We utilized gene set enrichment analysis (GSEA) to find potentially ADAMTS14-related pathways and applied univariate/multivariate Cox regression analyses to identify independent factors significantly related to overall survival (OS) for ccRCC. A nomogram consisted of independent prognostic factors was also conducted. We further explored the associations between ADAMTS14 with immunity and revealed its potential mechanisms. Results: ADAMTS14 displayed a higher expression in ccRCC tumor than in adjacent normal tissues, and further validated results of the ICGC dataset; qRT-PCR and immunohistochemistry remained consistent (all p < 0.05). Moreover, elevated ADAMTS14 expression was significantly associated with poor OS (p < 0.001). Through univariate/multivariate Cox regression analyses, ADAMTS14 was found to be an independent prognostic factor for ccRCC (both p < 0.05) and GSEA identified several signaling pathways including INSULIN, MTOR, and PPAR pathways. The nomogram based on independent prognostic factors was successfully established and well evaluated. Moreover, the expression of ADAMTS14 was remarkably associated with immune checkpoint molecules, tumor mutational burden (TMB), immune cells, and tumor immune microenvironment (all p < 0.05). Results from TIDE and TCIA showed that highly expressed ADAMTS14 could predict worse efficacy of immunotherapy (all p < 0.05). As for its potential mechanisms, we also revealed several LncRNA/RNA binding protein (RBP)/ADAMTS14 mRNA networks. Conclusions: ADAMTS14 was found to play oncogenic roles in ccRCC and to be significantly associated with immunity. Several LncRNA/RBP/ADAMTS14 mRNA networks were also identified for its potential mechanisms. [ABSTRACT FROM AUTHOR]

BackgroundADAMTS14 played a crucial role in the formation and development of various cancers. Currently, no associations had been revealed between ADAMTS14 and clear cell renal cell carcinoma (ccRCC). Hence, this study was designed to assess the prognostic values and immunological roles of ADAMTS14 in ccRCC and to reveal its potential mechanisms.MethodsADAMTS14-related expression profiles and related clinical data were downloaded from The Cancer Genome Atlas (TCGA) dataset, validated by the ICGC dataset, qRT-PCR, and immunohistochemistry. We utilized gene set enrichment analysis (GSEA) to find potentially ADAMTS14-related pathways and applied univariate/multivariate Cox regression analyses to identify independent factors significantly related to overall survival (OS) for ccRCC. A nomogram consisted of independent prognostic factors was also conducted. We further explored the associations between ADAMTS14 with immunity and revealed its potential mechanisms.ResultsADAMTS14 displayed a higher expression in ccRCC tumor than in adjacent normal tissues, and further validated results of the ICGC dataset; qRT-PCR and immunohistochemistry remained consistent (all p < 0.05). Moreover, elevated ADAMTS14 expression was significantly associated with poor OS (p < 0.001). Through univariate/multivariate Cox regression analyses, ADAMTS14 was found to be an independent prognostic factor for ccRCC (both p < 0.05) and GSEA identified several signaling pathways including INSULIN, MTOR, and PPAR pathways. The nomogram based on independent prognostic factors was successfully established and well evaluated. Moreover, the expression of ADAMTS14 was remarkably associated with immune checkpoint molecules, tumor mutational burden (TMB), immune cells, and tumor immune microenvironment (all p < 0.05). Results from TIDE and TCIA showed that highly expressed ADAMTS14 could predict worse efficacy of immunotherapy (all p < 0.05). As for its potential mechanisms, we also revealed several LncRNA/RNA binding protein (RBP)/ADAMTS14 mRNA networks.ConclusionsADAMTS14 was found to play oncogenic roles in ccRCC and to be significantly associated with immunity. Several LncRNA/RBP/ADAMTS14 mRNA networks were also identified for its potential mechanisms.

Acute myeloid leukaemia (AML) is a blood cancer with a heterogeneous genomic landscape. This study aimed to mine bioinformatics data generated by RNA sequencing to unveil an AML case transcriptome profile and identify novel therapeutic targets and markers. In this study, we have determined the transcriptomic profile and analysed gene variants of an AML patient at the time of diagnosis and validated some genes by quantitative reverse transcriptase polymerase chain reaction. ADAMTS14, ARHGAP22, and ependymin-related protein 1 (EPDR1) were markedly upregulated compared to the corresponding control. In addition, novel exonic single-nucleotide and insertion/deletion variants were identified in these genes. Hence, ADAMTS14, ARHGAP22, and EPDR1 can be proposed as potential novel targets in AML, and their exact roles should be further explored.

A disintegrin and metalloproteinase with thrombospondin motif 14 (ADAMTS14) is a member of the zinc-dependent protease family that is implicated in the occurrence and progression of tumors. Oral cancer (OC) is a common cancer worldwide, but it is particularly prevalent in Taiwan. However, whether the expression of ADAMTS14 is correlated with the carcinogenesis and progression of oral squamous cell carcinoma (OSCC) has not yet been investigated. In this study, we used immunohistochemistry (IHC) to examine 250 OSCC specimens in order to identify correlations between the cytoplasmic expression of ADAMTS14 and (1) clinicopathological features of OSCC as well as (2) clinical outcomes of OSCC. Our results indicate that cytoplasmic expression of ADAMTS14 was lower in OSCC tissues than in normal tissues. In analyzing correlations between ADAMTS14 expression and clinicopathological features, we found that negative cytoplasmic expression of ADAMTS14 was significantly associated with higher frequencies of lymph node metastasis and more advanced AJCC stages (III/IV). Kaplan−Meier survival analysis revealed that negative cytoplasmic expression of ADAMTS14 was also associated with significantly worse OSCC survival. Univariate and multivariate analyses confirmed that cytoplasmic expression of ADAMTS14 was associated with lymph node metastasis, tumor stage, and tumor grade and also indicated that cytoplasmic ADAMTS14 expression may be an independent prognostic factor for OSCC. This is the first study to report that the cytoplasmic expression level of ADAMTS14 is associated with OSCC prognosis and tumor progression. Our data indicate that ADAMTS14 can serve as a prognostic marker and a potential therapeutic target for OSCC.

Chondrosarcoma is one of the most common bone tumors, and at present, there is no non-invasive treatment option for this cancer. The chondrosarcoma OUMS-27 cell line produces proteoglycan and type II, IX, and XI collagens, which constitutes cartilage tissue. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) proteases are a group of secreted proteases, which include the procollagen N-proteinases ADAMTS-2, -3 and -14. These procollagen N-proteinases perform a role in the processing of procollagens to collagen and the maturation of type I collagen. The present study aimed to improve the understanding of the causes of metastasis, local invasion and resistance to chemo- and radiotherapy in chondrosarcoma, as well as the effect of insulin on cancer cells. The present study was designed to reveal the effects of insulin on procollagen N-proteinases in chondrosarcoma OUMS-27 cells. The cells were cultured in Dulbecco's modi- fied Eagle's medium (DMEM) alone or in DMEM containing 10 µg/ml insulin. The medium was changed every other day for 11 days. The cells were harvested on days 1, 3, 7 and 11, and total RNA isolation was performed immediately following harvesting. The expression levels of ADAMTS2, ADAMTS3 and ADAMTS14 mRNA were estimated by reverse transcription-quantitative polymerase chain reaction using appropriate primers. ADAMTS2 mRNA expression was found to be decreased on day 7 (P=0.028) and increased at day 11 compared with the control group (P=0.016). The increase in mRNA concentration at day 11 was significantly different compared to the concentrations on days 3 (P=0.047) and 7 (P=0.008). The expression of ADAMTS3 mRNA decreased immediately subsequent to insulin induction on day 1 compared with the control group (P=0.008). The most evident decrease in mRNA concentration was seen at day 7 subsequent to insulin induction (P=0.008). The present results demonstrated that ADAMTS2 and ADAMTS3 may perform a role in the invasion and metastasis of tumors, and may also possess proteolytic activity that results in the breakdown of the extracellular matrix (ECM). Insulin itself can modulate the biosynthesis of ECM macromolecules that are altered in diabetes through various pathways. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignant tumors of digestive system, and its main cause of death is tumor metastasis. The occurrence of CRC is a polygenic and multi-step complex process involving genetic and epigenetic alterations. It has been demonstrated that ADAMTS14 (A disintegrin and metalloproteinase with thrombospondin motifs 14) was hypermethylated in esophageal cancer using whole-genome methylation microarray in our previous report. The present study revealed that ADAMTS14 was highly methylated accompanied with low expression in CRC. In addition, demethylation agent 5-Aza-dC could demethylate ADAMTS14 promoter region and reactivate ADAMTS14 expression effectively in vitro. Therefore, promoter hypermethylation was probably contributed to ADAMTS14 epigenetic silencing in CRC. Furthermore, ADAMTS14 protein expression was higher at invasive tumor front than at the tumor center or other areas of tumor. Kaplan-meier survival analysis indicated that the high ADAMTS14 expression was correlated with poor prognosis in CRC patients, suggesting the possibility that ADAMTS14 is a promising indicator in the evaluation of CRC prognosis. [ABSTRACT FROM AUTHOR]

A disintegrin and metalloproteinase with thrombospondin motif 14 (ADAMTS14) is a member of the zinc-dependent protease family that is implicated in the occurrence and progression of tumors. Oral cancer (OC) is a common cancer worldwide, but it is particularly prevalent in Taiwan. However, whether the expression of ADAMTS14 is correlated with the carcinogenesis and progression of oral squamous cell carcinoma (OSCC) has not yet been investigated. In this study, we used immunohistochemistry (IHC) to examine 250 OSCC specimens in order to identify correlations between the cytoplasmic expression of ADAMTS14 and (1) clinicopathological features of OSCC as well as (2) clinical outcomes of OSCC. Our results indicate that cytoplasmic expression of ADAMTS14 was lower in OSCC tissues than in normal tissues. In analyzing correlations between ADAMTS14 expression and clinicopathological features, we found that negative cytoplasmic expression of ADAMTS14 was significantly associated with higher frequencies of lymph node metastasis and more advanced AJCC stages (III/IV). Kaplan–Meier survival analysis revealed that negative cytoplasmic expression of ADAMTS14 was also associated with significantly worse OSCC survival. Univariate and multivariate analyses confirmed that cytoplasmic expression of ADAMTS14 was associated with lymph node metastasis, tumor stage, and tumor grade and also indicated that cytoplasmic ADAMTS14 expression may be an independent prognostic factor for OSCC. This is the first study to report that the cytoplasmic expression level of ADAMTS14 is associated with OSCC prognosis and tumor progression. Our data indicate that ADAMTS14 can serve as a prognostic marker and a potential therapeutic target for OSCC. [ABSTRACT FROM AUTHOR]

To investigate the association between single nucleotide polymorphisms (SNPs) of A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 14 ( ADAMTS14 ) gene and susceptibility to knee osteoarthritis (KOA) in Chinese Han population. Using a case-control design, we enrolled 346 KOA patients and 480 healthy controls. Peripheral blood samples were extracted from each subject. Genotype was determined by sequencing PCR products. The genotype frequencies between cases and controls were compared. The genotype distribution was in accordance with Hardy-Weinberg equilibrium. The minor G allele in case group was significantly higher than in the control group (21.4 compared with 8.8%, P =0.000, odds ratio (OR) = 1.71 (95% confidence interval (CI): 1.39-2.11). The GG genotype and the GG/AG combination were more common in the osteoarthritis (OA) group than in the control group. Compared with AA genotype, the GG (OR = 3.09, 95%CI: 2.01-4.75), AG (OR = 2.55, 95%CI: 1.64-3.96), and GG/AG (OR = 1.57, 95%CI: 1.19-2.07) increased the risk of OA. Multiple logistic confirmed the findings by adjusting some potential factors. Subgroup analysis indicated that the ras4747096 was still significantly associated with KOA. There were no significant differences in allele frequency or genotypes frequency for erythrocyte sedimentation rate and C-reaction protein in OA patients ( P >0.05). ADAMTS14 gene polymorphism was associated with KOA, and the GG genotype increased the risk of KOA in Chinese Han population. The ADAMTS14 may be a diagnostic marker and therapeutic target for KOA treatment. The future study should explore the specific molecular mechanism., (© 2018 The Author(s).)