The progressive degradation in the trabecular meshwork (TM) is related to age-related ocular diseases like primary open-angle glaucoma. However, the molecular basis and biological significance of the aging process in TM have not been fully elucidated. Here, we established a dynamic single-cell transcriptomic landscape of aged macaque TM, wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM aging. Furthermore, we divided TM cells into 13 clusters and performed an in-depth analysis on cluster 0, which had the highest aging score and the most significant changes in cell proportions between the two groups. Ultimately, we found that the APOE gene was an important differentially expressed gene in cluster 0 during the aging process, highlighting the close relationship between cell migration and extracellular matrix regulation, and TM function. Our work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components, thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal range. Our work provides valuable insights for future clinical diagnosis and treatment of glaucoma.

Objective To study the validity of acoustic voice quality index（AVQI） in Mandarin Chinese language, to investigate the accuracy of AVQI in discriminating normal and dysphonic voice, and the accuracy in discriminating across the perceptual categories of dysphonia severity. Methods This study included 59 subjects with normal voice and 217 subjects with dysphonic. Voice samples of sustained vowel/a/and continuous speech were collected. AVQI was calculated using AVQI（v02.06） script in Praat software. G score of GRBAS system was assessed by 5 raters and the mean value was used in following analysis. Spearman correlation coefficient was calculated. ROC curves were drawn to evaluate the accuracy of discriminating normal and dysphonic voice, and discriminating across the perceptual categories of dysphonia severity. Results The correlation coefficient of AVQI and Gmean was 0.756（P＜0.001）. When discriminating normal and dysphonic voice at Gmean=0.2, AUC=0.849 and threshold was 2.905. When discriminating them under clinical diagnosis, AUC was 0.788 and threshold was 3.18. When discriminating voice of different severity, AUC and threshold of normal vs slight were 0.770 and 1.985 respectively. Those of slight vs moderate were 0.755 and 4.17, and those of moderate vs severe were 0.799 and 6.36 respectively. Conclusion The AVQI is an easy-to-use and quick tool for the objective measure of overall voice quality in Mandarin Chinese language. It could discriminate normal and dysphonic voice, and the voice with different dysphonia severity to a certain extent.

Objective Studies showed that photodynamic therapy (PDT) might be able to prevent vocal fold scar formation when treating laryngeal lesions. We aim to investigate if PDT improves vocal wound healing and reduces scar formation in both prophylactic and remodeling procedures performed in vivo . Study Design In vivo . Methods Vocal fold stripping was performed in Sprague–Dawley rats. PDT was performed with intraperitoneal injection of 100 mg/kg 5‐Aminolevulinic Acid (5‐ALA) and 635 nm laser irradiation of 20, 40, and 60 J/cm 2 . PDT was performed immediately after surgery to study the prophylactic effect and 4 weeks after surgery to study the remodeling effect. Gene expression was evaluated with real‐time PCR at 1 week after PDT. Histologic evaluations were performed 12 weeks after PDT, including hematoxylin–eosin, Masson, Alcian blue staining, and immunohistochemical staining of collagen I and III. Results PDT induced similar effects on the vocal fold wound healing outcomes in both prophylactic and remodeling procedures. Expression of MMP8, MMP13, HAS2, and TGFβ1 was significantly elevated. Histologic evaluation revealed significantly increased thickness, decreased density of collagen, and increased deposition of hyaluronic acid in the lamina propria. Immunohistochemistry also revealed better distribution and reduced density of collagen I and III. The most obvious changes were seen in the 60 J/cm 2 PDT group. Conclusion PDT could significantly improve vocal wound healing by providing both prophylactic effects and remodeling effects. It may be a minimally invasive treatment for vocal fold lesions with slight vocal scarring, and may be used to treat acute or chronic vocal injury to reduce vocal scarring. Level of Evidence N/A Laryngoscope , 133:1943–1951, 2023

目的 分析未经嗓音训练或改变音调手术治疗的跨性别女性的嗓音特点,探讨其与顺性别人群的差异.方法 选择78例未经嗓音训练或改变音调手术的跨性别女性为研究对象,以顺性别男性和女性各30例为对照组,分别采集汉语习惯性言语样本和发元音/a/、/i/声样本,分析言语平均基频(SFF)、最高言语基频(H-SFF)、最低言语基频(L-SFF),元音/a/的最高基频、最低基频、jitter、shimmer、最长发声时间(M PT)以及元音/a/、/i/的第1、2、3共振峰(F1、F2、F3)频率.另招募男性、女性志愿者各10例,对所有受试者的嗓音进行女性化程度主观听觉评估(1～2分为女性化嗓音,3～5分为中性化嗓音,6～7分为男性化嗓音).结果 跨性别女性的SFF、H-SFF均显著高于男性对照组(P<0.01),低于女性对照组(P<0.01),但音域范围与男性对照组无明显差异(P>0.05);跨性别女性组MPT显著小于男性对照组(P<0.01),与女性对照组差异无统计学意义(P>0.05);跨性别女性组的元音/a/、/i/的F2、F3频率显著高于男性对照组(P<0.01),元音/a/的F2、元音/i/的F1低于女性对照组(P<0.05).跨性别女性组的嗓音女性化程度评分(3.397±1.36分)介于男性(6.138±0.58分)和女性对照组(1.75±0.61分)之间.结论 本组跨性别女性的嗓音特征介于顺性别男性与女性之间,未经嗓音训练或改变音调手术治疗的跨性别女性难以达到女性的嗓音条件和性别认同,该类群体可能存在改变嗓音的诉求.

The aim of the present study was to integrate all the eligible studies and investigate whether the transforming growth factor-b1 (TGF-b1) gene polymorphisms (TGF-b1 T869C and TGF-b1 T29C) are correlated with postmenopausal osteoporosis (PMOP) risk. PMOP is a common skeletal disease and several genetic factors play an important role in the development and progression of PMOP. Significant associations between TGF-b1 gene polymorphisms (TGFb1 T869C and TGF-b1 T29C) and PMOP risk have been reported; however, some of these results are controversial. A systematic online search was performed using PubMed, EMBASE, Web of Science, and the Cochrane Library to identify case–control studies investigating the relationship between TGF-b1 T869C and TGF-b1 T29C polymorphisms and the susceptibility of PMOP. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the associations, and subgroup meta-analyses were performed according to the ethnicity of the study populations. Eight studies involving 1851 cases and 2247 controls met the inclusion criteria after assessment by 2 reviewers. Overall, there were significant associations between TGF-b1 T869C and TGF-b1 T29C polymorphisms and PMOP (TGF-b1 T869C—C vs T: OR1⁄4 1.18, 95% CI1⁄4 1.02–1.36, P1⁄4 0.030; CC vs TT: OR1⁄4 1.38, 95% CI1⁄4 1.01–1.88, P1⁄4 0.042; CC vs CT/TT: OR1⁄4 1.39, 95% CI1⁄4 1.09–1.76, P1⁄4 0.008; TGF-b1 T29C—CT vs TT: OR1⁄4 1.25, 95% CI1⁄4 1.02–1.53, P1⁄4 0.032; CT/CC vs TT: OR1⁄4 1.37, 95% CI1⁄4 1.02–1.84, P1⁄4 0.035). In the subgroup analysis of ethnicity, significant association was observed between TGF-b1 T869C polymorphism and PMOP risk in Asian population (C vs T: OR1⁄4 1.18, 95% CI1⁄4 1.01–1.38, P1⁄4 0.043; CC vs TT: OR1⁄4 1.41, 95% CI1⁄4 1.01–1.97, P1⁄4 0.047; CT/CC vs TT: OR1⁄4 1.31, 95% CI1⁄4 1.03– 1.66, P1⁄4 0.026; CC vs CT/TT: OR1⁄4 1.35, 95% CI1⁄4 1.03–1.75, P1⁄4 0.028); however, there was no significant association between TGF-b1 T869C polymorphism and PMOP risk in Caucasian population. With regard to TGF-b1 T29C polymorphism, significant association was also observed in Asian population (CT vs TT: OR1⁄4 1.37, 95% CI1⁄4 1.07– 1.75, P1⁄4 0.013; CT/CC vs TT: OR1⁄4 1.54, 95% CI1⁄4 1.16–2.05, P1⁄4 0.003), while there was no significant association in Caucasian population. The TGF-b1 T869C and TGF-b1 T29C polymorphisms may be involved in susceptibility to PMOP, particular in Asian patients. (Medicine 94(4):e461) Abbreviations: BMD = bone mineral density, HWE = Hardy– Weinberg equilibrium, PMOP = postmenopausal osteoporosis. INTRODUCTION P ostmenopausal osteoporosis (PMOP) is the most common bone disease, and features bone loss and susceptibility to fragility fractures that are associated with a low bone mineral density (BMD). PMOP is among the most prevalent metabolic bone diseases in postmenopausal women. Although PMOP has been described decades ago, its exact mechanisms remain poorly understood. Genetic or acquired disorders can compromise gains in bone quantity and quality leading to osteoporosis early in life. Previous studies indicated that low BMD was a major risk factor for PMOP and was highly heritable. Besides, many association studies have shown that genes and genetic factors might be involved in the pathogenesis of PMOP. Recently, many studies deduced that transforming growth factor superfamily catalyzed enzymes for osteoporosis. Transforming growth factor-b1 (TGF-b1), a member of the transforming growth factor superfamily, is abundant in bone and has been implicated as an important regulator of both bone formation and resorption, which can stimulate proliferation or differentiation of preosteoblasts as well as inhibit mature osteoclasts and proliferation of mononuclear osteoclast precursors in vitro. Molecular biological evidence showed that polymorphisms in the TGF-b result in a Leu!Pro substitution at amino acid 10, which includes a T!C transition at nucleotide 29 and a T!C transition at nucleotide 869 in the region encoding the signal sequence. This change influenced the bone remodeling, indicating that genetic polymorphisms of the T29C and T869C genes might be associated with increased risk for osteoporosis. Recently, significant association has been found between TGF-b1 T869C and TGF-b1 T29C polymorphisms and PMOP in several studies. But the results of these studies are complex and even opposite. Furthermore, no consolidated reports have been conducted to investigate the associations between TGF-b1 T869C and TGF-b1 T29C polymorphisms and PMOP. Therefore, we performed this Editor: James Franklin Kellam. Received: December 6, 2014; revised: December 19, 2014; accepted: December 22, 2014. From the Department of Orthopaedic Surgery (JS, CZ, LX, HY), The First Affiliated Hospital of Soochow University; and Department of Orthopaedics (MY), Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China. Correspondence: Huilin Yang, No. 188 Shizi Street, Suzhou 215006, China (e-mail: orthopaedicvit@163.com). JS and CZ contributed equally to this work. This research was funded by Natural Science Foundation of China (81171689) and Jiangsu Provincial Special Program of Medical Science, China (BL2012004). The authors have no conflicts of interest to disclose. Copyright # 2015 Wolters Kluwer Health, Inc. All rights reserved. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be changed in any way or used commercially. ISSN: 0025-7974 DOI: 10.1097/MD.0000000000000461 Medicine Volume 94, Number 4, January 2015 www.md-journal.com | 1 meta-analysis to make contribution to obtain a more exact evaluation of the associations between TGF-b1 T869C and TGF-b1 T29C polymorphisms and PMOP risk. MATERIALS AND METHODS Literature Search Databases including PubMed, EMBASE, Web of Science, and the Cochrane Library were searched for the eligible case– control studies that examined the relationship between TGF-b1 polymorphisms (TGF-b1 T869C and TGF-b1 T29C) and the susceptibility to PMOP. The following search terms were used: (Postmenopausal osteoporosis OR PMOP) AND (Transforming growth factor-b1 OR TGF-b1 OR TGF-b1 T869C OR TGF-b1 T29C) AND (polymorphism OR single nucleotide polymorphism OR SNP OR variation). There were no language restrictions in our study selection. Secondary searches of unpublished literature were conducted by searching the reference lists of the selected studies and reviews. Inclusion and Exclusion Criteria The inclusion criteria of our meta-analysis were as follows: case–control study; evaluation of PMOP risk and at least one of these identified TGF-b1 gene polymorphisms (TGF-b1 T869C and TGF-b1 T29C); and sufficient data, including number or frequency of alleles and genotypes. The exclusion criteria were reviews or case reports that were not case–control studies, no available data reported, and duplicated reports. Data Extraction Data from the eligible studies were extracted according to the inclusion and exclusion criteria by 2 authors, and a consensus was reached. For each study, the following data were collected: author list, year of publication, ethnicity, sample size, alleles, and genotypes of TGF-b1 T869C and TGF-b1 T29C polymorphisms. Furthermore, we also evaluated whether the genotype distributions of the control group followed the Hardy– Weinberg equilibrium (HWE). Data Synthesis and Statistical Analysis Odds ratio (OR) and 95% confidence interval (CI) were calculated to evaluate the association between TGF-b1 T869C and TGF-b1 T29C polymorphisms and PMOP risk. Allele contrast (C vs T), heterozygote (CT vs TT), homozygote (CC vs TT), dominant (CT/CC vs TT), and recessive (CC vs CT/TT) models were used to evaluate the relationship between TGF-b1 T869C and TGF-b1 T29C polymorphisms and PMOP risk. The assumption that there was heterogeneity was verified by a x-based Q statistical test and quantified by I metric value. If I value is >50% or P< 0.10, suggesting that an obvious heterogeneity existed, ORs were pooled by random effect model; otherwise, the fixed effect model was used. Sensitivity analysis was performed to assess the impact of each study on the combined effect of the present meta-analysis and subgroup analysis was performed according to the ethnicity of the study populations. All metaanalyses were performed using Stata 12.0 software (StataCorp, College Station, TX) and a P value below 0.05 was considered statistically significant. This is a systematic review about literatures, so ethical approval was not necessary for our research. RESULTS Study Characteristics A total of 8 studies involving 1851 cases and 2247 controls eventually satisfied the eligibility criteria (Figure 1). Three studies reported both alleles and genotypes of Records identified through database searching (n = 56) pubMed: 25, EMBASE:31 Additional records identified trhough other sources (n = 2) Records after duplicates removed (n = 23) Records screened (n = 23) Records excluded (n = 10) 10 studies did not meet the aim of our study Full-text articles excluded (n = 5) 5, no sufficient data 4 studies reported TGF-β1 T869C 4 studies reported TGF-β1 T29C Full-text articles assessed for eligibility (n = 13) Studies included in metaanalysis (n = 8) FIGURE 1. The study selection and inclusion process. Sun et al Medicine Volume 94, Number 4, January 2015 2 | www.md-journal.com Copyright # 2015 Wolters Kluwer Health, Inc. All rights reserved. TABLE 1. General Characteristics of Studies Included in the Meta-Analysis Author Year Ethnicity Sample Size TGF-b1 T869C Case TGF-b1 T869C Control TGF-b1 T29C Case TGF-b1 T29C Control Case Control C/T CC/TC/TT C/T CC/TC/TT C/T CC/TC/TT C/T CC/TC/TT Tural et al 2013 Caucasian 146 97 167/125 50/67/29 104/90 24/56/17 Yamada et al 2001 Asian 288 625 276/300 58/160/70 536/71

Background: To investigate the value of the standard deviation of the fundamental frequency (F-0 SD), jitter, and shimmer for the evaluation of voice quality and the description of vocal characteristics in patients with voice disorders. Methods: This prospective cohort study included 4 groups: vocal cord polyps (VCP) group (n=55), early-stage (stage I-II) laryngeal carcinoma (ELC) group (n=35), mutational falsetto (MF) group (n=17), and a normal control group (n=29). The participants were asked to emit a sustained vowel /a/ and raise the pitch gradually. Acoustic parameters, including F-0, F0SD, jitter, and shimmer, were recorded and analyzed. Results: The F0SD was highest in the MF group. The F0SD in the MF group and the ELC group was significantly higher than that in the VCP group and the control group (P<0.05), and the F0SD in the VCP group was significantly higher than that in the control group (P<0.05). However, there was no significant difference in F0SD between the MF group and the ELC group (P>0.05). The jitter and shimmer in the ELC group were significantly higher compared to the other groups (P<0.05), and the jitter and shimmer in the VCP group were significantly higher than those in the MF group and the control group (P<0.05). There were no significant differences in jitter or shimmer between the MF group and the control group (P>0.05). Conclusions: F0SD, jitter, and shimmer are important parameters for the evaluation of pitch variation during sustained phonations, and can discriminate between MF and voice disorders.

Hearing loss is one of the most common sensory disorders in newborns and is mostly caused by genetic factors. Autosomal recessive nonsyndromic hearing loss (ARNSHL) is usually characterized as a severe-to-profound congenital sensorineural hearing loss and later can cause various degrees of defect in the language and intelligent development of newborns. The mutations in LOXHD1 gene have been shown to cause DFNB77, a type of ARNSHL. To date, there are limited reports about the association between LOXHD1 gene and ARNSHL. In this study, we reported six patients from four Chinese families suffering from severe-to-profound nonsyndromic hearing loss. We performed targeted next generation sequencing in the six affected members and identified five novel pathogenic mutations in LOXHD1 including c.277G>A (p.D93N), c.611-2A>T, c.1255+3A>G, c.2329C>T (p.Q777∗), and c.5888delG (p.G1963Afs∗136). These mutations were confirmed to be cosegregated with the hearing impairment in the families by Sanger sequencing and were inherited in an autosomal recessive pattern. All of the five mutations were absent in 200 control subjects. There were no symptoms of Fuchs corneal dystrophy in the probands and their blood-related relatives. We concluded that these five novel mutations could be involved in the underlying mechanism resulting in the hearing loss, and this discovery expands the genotypic spectrum of LOXHD1 mutations.

Aluminum (Al) recognized as a persistent environmental contaminant is associated with bone diseases. Nicotinamide mononucleotide (NMN) is an intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis widely used to replenish NAD+. Increasing evidences demonstrated that replenishment of NAD+ can protect against bone loss. However, the potentially protective effects of NMN against Al-induced bone impairment and the underlying mechanisms remain unknown. In the present study, we sought to investigate the protective effects of NMN on Al-induced bone damages and elucidate the potential mechanisms. We orally exposed AlCl3 (10 mg/L) to Sprague-Dawley rats in drinking water for 12 weeks while NMN (20 mg/kg) were intraperitoneally injected in last 4 weeks. We found that Al could induce bone damages, bone loss and oxidative stress. In addition, we showed that Al triggered inflammatory responses, which is mediated by the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation. However, NMN treatment significantly alleviated Al-induced bone injuries by decreasing bone loss, suppressing oxidative stress as well as inhibiting Thioredoxin-interacting protein (TXNIP)-NLRP3 inflammasome pathway and pro-inflammatory cytokine production in vivo and in vitro. Meanwhile, treatment with TXNIP siRNA performed the same protective effects as NMN in Al-treated MC3T3-E1 cells. Collectively, our results suggest that NMN may reduce Al-induced bone loss partly by suppression of the TXNIP-NLRP3 inflammasome pathway.

Nogo-B receptor (NgBR) is a type I receptor with a single transmembrane domain and specifically binds to ligand Nogo-B. A previous study demonstrated that NgBR was highly expressed in human breast invasive ductal carcinoma and promoted epithelial-mesenchymal transition in breast tumor cells. Our recent work found that NgBR expression was associated with a poor prognosis in human patients with hepatocellular carcinoma (HCC). Here, we elucidate that the increased expression of NgBR contributes toward the increased cell growth of human HCC cells both in vitro and in vivo. Cell viability and clonogenic survival analysis results demonstrated that knockdown of NgBR inhibits the cell growth in human HCC cells, which correlates with a reduction in the phosphorylation of Akt levels. Furthermore, overexpression of NgBR by the cotransfected pIRES-NgBR plasmid together with NgBR siRNA in human HCC cells can rescue impaired phosphorylation of Akt levels in NgBR knockdown human HCC cells. In addition, cell viability analyses showed that NgBR overexpression can rescue the cell growth inhibition presented in human HCC NgBR knockdown cells. Taken together, our results suggest that NgBR potentially acts as an oncogene in HCC by increasing Akt activity. Thus, NgBR may represent a new potential diagnostic and therapeutic target for the treatment of HCC.

POU4F3 gene encodes a transcription factor which plays an essential role in the maturation and maintenance of hair cells in cochlea and vestibular system. Several mutations of POU4F3 have been reported to cause autosomal dominant nonsyndromic hearing loss in recent years. In this study, we describe a pathogenic nonsense mutation located in POU4F3 in a four-generation Chinese family. Target region capture sequencing was performed to search for the candidate mutations from 81 genes related to nonsyndromic hearing loss in this family. A novel nonsense mutation of POU4F3 , c.337C>T (p.Gln113⁎), was identified in a Chinese family characterized by late-onset progressive nonsyndromic hearing loss. The novel mutation cosegregated with hearing loss in this family and was absent in 200 ethnicity-matched controls. The mutation led to a stop codon and thus a truncated protein with no functional domains remained. Transient transfection and immunofluorescence assay revealed that the subcellular localization of the truncated protein differed markedly from normal protein, which could be the underlying reason for complete loss of its normal function. Here, we report the first nonsense mutation of POU4F3 associated with progressive hearing loss and explored the possible underlying mechanism. Routine examination of POU4F3 is necessary for the genetic diagnosis of hereditary hearing loss in the future.

Glutamate is an important excitatory neurotransmitter in mammalian brains, but excessive amount of glutamate can cause “excitotoxicity” and lead to neuronal death. As bipolar neurons, spiral ganglion neurons (SGNs) function as a “bridge” in transmitting auditory information from the ear to the brain and can be damaged by excessive glutamate which results in sensorineural hearing loss. In this study, edaravone, a free radical scavenger, elicited both preventative and therapeutic effects on SGNs against glutamate-induced cell damage that was tested by MTT assay and trypan blue staining. Ho.33342 and PI double staining revealed that apoptosis as well as necrosis took place during glutamate treatment, and apoptosis was the main type of cell death. Oxidative stress played an important role in glutamate-induced cell damage but pretreatment with edaravone alleviated cell death. Results of western blot demonstrated that mechanisms underlying the toxicity of glutamate and the protection of edaravone were related to the PI3K pathway and Bcl-2 protein family.

The aim of the present study was to integrate all the eligible studies and investigate whether the transforming growth factor-beta 1 (TGF-beta 1) gene polymorphisms (TGF-beta 1 T869C and TGF-beta 1 T29C) are correlated with postmenopausal osteoporosis (PMOP) risk.PMOP is a common skeletal disease and several genetic factors play an important role in the development and progression of PMOP. Significant associations between TGF-beta 1 gene polymorphisms (TGF-beta 1 T869C and TGF-beta 1 T29C) and PMOP risk have been reported; however, some of these results are controversial.A systematic online search was performed using PubMed, EMBASE, Web of Science, and the Cochrane Library to identify case-control studies investigating the relationship between TGF-beta 1 T869C and TGF-beta 1 T29C polymorphisms and the susceptibility of PMOP. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the associations, and subgroup meta-analyses were performed according to the ethnicity of the study populations.Eight studies involving 1851 cases and 2247 controlsmet the inclusion criteria after assessment by 2 reviewers. Overall, there were significant associations between TGF-beta 1 T869Cand TGF-beta 1 T29C polymorphisms and PMOP (TGF-beta 1 T869C-C vs T: OR = 1.18, 95% CI = 1.02-1.36, P = 0.030; CC vs TT: OR = 1.38, 95% CI = 1.01-1.88, P = 0.042; CC vs CT/TT: OR = 1.39,95% CI = 1.09-1.76, P = 0.008; TGF-beta 1T29C-CT vs TT: OR = 1.25, 95% CI = 1.02-1.53, P = 0.032; CT/CC vs TT: OR = 1.37, 95% CI = 1.02-1.84, P = 0.035). In the subgroup analysis of ethnicity, significant association was observed between TGF-beta 1 T869C polymorphism and PMOP risk in Asian population (C vs T: OR = 1.18, 95% CI = 1.01-1.38, P = 0.043; CC vs TT: OR = 1.41, 95% CI = 1.01-1.97, P = 0.047; CT/CC vs TT: OR = 1.31, 95% CI = 1.03-1.66, P = 0.026; CC vs CT/TT: OR = 1.35, 95% CI = 1.03-1.75, P = 0.028); however, there was no significant association between TGF-beta 1 T869C polymorphism and PMOP risk in Caucasian population. With regard to TGF-beta 1 T29C polymorphism, significant association was also observed inAsian population (CTvsTT: OR = 1.37, 95% CI = 1.07-1.75, P = 0.013; CT/CC vs TT: OR = 1.54, 95% CI = 1.16-2.05, P = 0.003), while there was no significant association in Caucasian population.The TGF-beta 1 T869C and TGF-beta 1 T29C polymorphisms may be involved in susceptibility to PMOP, particular in Asian patients.

AbstractThe aim of the present study was to integrate all the eligible studies and investigate whether the transforming growth factor-&bgr;1 (TGF-&bgr;1) gene polymorphisms (TGF-&bgr;1 T869C and TGF-&bgr;1 T29C) are correlated with postmenopausal osteoporosis (PMOP) risk.PMOP is a common skeletal disease and several genetic factors play an important role in the development and progression of PMOP. Significant associations between TGF-&bgr;1 gene polymorphisms (TGF-&bgr;1 T869C and TGF-&bgr;1 T29C) and PMOP risk have been reported; however, some of these results are controversial.A systematic online search was performed using PubMed, EMBASE, Web of Science, and the Cochrane Library to identify case–control studies investigating the relationship between TGF-&bgr;1 T869C and TGF-&bgr;1 T29C polymorphisms and the susceptibility of PMOP. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the associations, and subgroup meta-analyses were performed according to the ethnicity of the study populations.Eight studies involving 1851 cases and 2247 controls met the inclusion criteria after assessment by 2 reviewers. Overall, there were significant associations between TGF-&bgr;1 T869C and TGF-&bgr;1 T29C polymorphisms and PMOP (TGF-&bgr;1 T869C—C vs T: OR = 1.18, 95% CI = 1.02–1.36, P = 0.030; CC vs TT: OR = 1.38, 95% CI = 1.01–1.88, P = 0.042; CC vs CT/TT: OR = 1.39, 95% CI = 1.09–1.76, P = 0.008; TGF-&bgr;1 T29C—CT vs TT: OR = 1.25, 95% CI = 1.02–1.53, P = 0.032; CT/CC vs TT: OR = 1.37, 95% CI = 1.02–1.84, P = 0.035). In the subgroup analysis of ethnicity, significant association was observed between TGF-&bgr;1 T869C polymorphism and PMOP risk in Asian population (C vs T: OR = 1.18, 95% CI = 1.01–1.38, P = 0.043; CC vs TT: OR = 1.41, 95% CI = 1.01–1.97, P = 0.047; CT/CC vs TT: OR = 1.31, 95% CI = 1.03–1.66, P = 0.026; CC vs CT/TT: OR = 1.35, 95% CI = 1.03–1.75, P = 0.028); however, there was no significant association between TGF-&bgr;1 T869C polymorphism and PMOP risk in Caucasian population. With regard to TGF-&bgr;1 T29C polymorphism, significant association was also observed in Asian population (CT vs TT: OR = 1.37, 95% CI = 1.07–1.75, P = 0.013; CT/CC vs TT: OR = 1.54, 95% CI = 1.16–2.05, P = 0.003), while there was no significant association in Caucasian population.The TGF-&bgr;1 T869C and TGF-&bgr;1 T29C polymorphisms may be involved in susceptibility to PMOP, particular in Asian patients.