Genetic analysis of 15 STR loci in Chinese Han population from West China

Allele frequencies for 15 short tandem repeat （STR） loci （D8S1179, D21S11, D7S820, CSFIPO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, and FGA） were obtained from 7,636 unrelated individuals of Chinese Han population living in Qinghai and Chongqing, China. Totally 206 alleles were observed, with the corresponding allele frequencies ranging from 0.0001-0.4982. Chi-square test showed that all of the STR loci agreed with the Hardy-Weinberg equilibrium. We also compared our data with previously published population data of other ethnics or areas. The results are valuable for human identification and paternity testing in Chinese Han population.     

Polymorphism of rs873308 near the transmembrane protein 57 gene is associated with serum lipid levels

SNP (single-nucleotide polymorphism) of rs10903129 near the TMEM (transmembrane protein) 57 locus has been associated with TC (total cholesterol) in a previous GWAS (genome-wide association study), but the association of TMEM57 rs873308 SNP and serum lipid levels has not been previously reported. The current study was undertaken to detect the association of the TMEM57 rs873308 SNP and several environmental factors with serum lipid profiles in the Han Chinese and Mulao populations. The genotypes of the TMEM57 rs873308 SNP in 865 individuals of Han Chinese and 902 participants of Mulao nationality were determined by PCR and RFLP (restriction-fragment-length polymorphism) combined with gel electrophoresis and then confirmed by direct sequencing. The T allele frequency of TMEM57 rs873308 SNP was not different between Han and Mulao (23.18% versus 25.72%, P>0.05), but different between males and females in the two ethnic groups (P<0.05). The T allele carriers had lower serum TC, Apo (apolipoprotein) B, HDL-C (high-density lipoprotein cholesterol) levels, ApoA1/ApoB ratio in Han; and lower TAG (triacylglycerol), LDL-C (low-density lipoprotein cholesterol), ApoA1 levels and the ApoA1/ApoB ratio and higher HDL-C levels in Mulao than the T allele non-carriers. There was also different association of the TMEM57 rs873308 SNP and serum lipid profiles between males and females in the both ethnic groups. Serum lipid parameters in the two ethnic groups were also associated with several environmental factors. The association of the TMEM57 rs873308 SNP and serum lipid levels was different in the Han Chinese and Mulao populations and between males and females in the both ethnic groups. There may be a sex-specific association of the TMEM57 rs873308 SNP and serum lipid levels in our study populations.     

Novel insights into plasma biomarker candidates in patients with chronic mountain sickness based on proteomics

Chronic mountain sickness (CMS) is a progressive incapacitating syndrome induced by lifelong exposure to hypoxia. In the present study, proteomic analysis was used to identify the differentially expressed proteins (DEPs) and then evaluate the potential plasma biomarkers between CMS and non-CMS groups. A total of 145 DEPs were detected in CMS Han Chinese people who live in the plateau (CMS-HPu), among which 89 were significantly up-regulated and 56 were significantly down-regulated. GO enrichment analysis showed that various biological processes were enriched, including the hydrogen peroxide metabolic/catabolic process, reactive oxygen species (ROS) metabolic, and acute inflammatory response. Protein–protein interaction analysis showed that antioxidant activity, the hydrogen peroxide catabolic process and peroxidase activity were primarily mapped in interaction proteins. Nine modules showed significantly clustering based on WGCNA analysis, with two being the most significant, and GO analysis showed that proteins of both modules were primarily enriched in oxidative stress-related biological processes. Four DEPs increased in CMS patients were evaluated as the candidate biomarkers, and three showed significant AUC: hemoglobin β chain (HB-β), thioredoxin-1 (TRX1), and phosphoglycerate kinase 1 (PGK1). The present study provides insights into the pathogenesis of CMS and further evaluates the potentially biomarkers for its prevention and treatment of it.     

Identification of novel biomarkers in seasonal allergic rhinitis by combining proteomic, multivariate and pathway analysis

Background

Glucocorticoids (GCs) play a key role in the treatment of seasonal allergic rhinitis (SAR). However, some patients show a low response to GC treatment. We hypothesized that proteins that correlated to discrimination between symptomatic high and low responders (HR and LR) to GC treatment might be regulated by GCs and therefore suitable as biomarkers for GC treatment.

Methodology/Principal Findings

We identified 953 nasal fluid proteins in symptomatic HR and LR with a LC MS/MS based-quantitative proteomics analysis and performed multivariate analysis to identify a combination of proteins that best separated symptomatic HR and LR. Pathway analysis showed that those proteins were most enriched in the acute phase response pathway. We prioritized candidate biomarkers for GC treatment based on the multivariate and pathway analysis. Next, we tested if those candidate biomarkers differed before and after GC treatment in nasal fluids from 40 patients with SAR using ELISA. Several proteins including ORM (P<0.0001), APOH (P<0.0001), FGA (P<0.01), CTSD (P<0.05) and SERPINB3 (P<0.05) differed significantly before and after GC treatment. Particularly, ORM (P<0.01), FGA (P<0.05) and APOH (P<0.01) that belonged to the acute phase response pathway decreased significantly in HR but not LR before and after GC treatment.

Conclusions/Significance

We identified several novel biomarkers for GC treatment response in SAR with combined proteomics, multivariate and pathway analysis. The analytical principles may be generally applicable to identify biomarkers in clinical studies of complex diseases.     

肾病综合征患者血脂代谢紊乱与血胆红素和蛋白代谢指标的相关性分析

目的:研究肾病综合征(NS)患者血脂代谢紊乱与血胆红素和蛋白代谢指标的相关性。方法:纳入我院从2017年5月～2019年5月收治的NS患者50例进行研究,记作病变组,另取同期于我院进行体检的健康人员50例作为健康组。检测两组血脂代谢相关指标[甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)]、血胆红素相关指标[总胆红素(TBIL)、直接胆红素(DBIL)以及间接胆红素(IBIL)]以及蛋白代谢相关指标[血清总蛋白(TP)、血清清蛋白(ALB)、尿微量清蛋白(UALB)]水平并进行对比,予以Pearson相关性分析各指标之间的相关性。结果:病变组TG、TC、LDL-C、ApoA1、ApoB水平均显著高于健康组,而HDL-C水平显著低于健康组(均P0.05)。病变组TBIL、DBIL、IBIL水平均显著低于健康组(均P0.05)。病变组TP、ALB水平均显著低于健康组,而UALB水平显著高于健康组(均P0.05)。经Pearson相关性分析可得:NS患者TG、TC、LDL-C、ApoA1、ApoB与TBIL、DBIL、IBIL、TP、ALB均呈负相关(均P0.05);TG、TC、LDL-C、ApoA1、ApoB与UALB均呈正相关(均P0.05);HDL-C与TBIL、DBIL、IBIL、TP、ALB均呈正相关(均P0.05);HDL-C与UALB呈负相关(均P0.05)。结论:NS患者血脂代谢紊乱和血胆红素、蛋白代谢指标密切相关,血胆红素、蛋白代谢指标可能参与了NS患者血脂代谢紊乱的机制。     

Serum proteome mapping of EGF transgenic mice reveal mechanistic biomarkers of lung cancer precursor lesions with clinical significance for human adenocarcinomas

Atypical adenomatous hyperplasia (AAH) of the lung is a pre-invasive lesion (PL) with high risk of progression to lung cancer (LC). However, the pathways involved are uncertain. We searched for novel mechanistic biomarkers of AAH in an EGF transgenic disease model of lung cancer. Disease regulated proteins were validated by Western immunoblotting and immunohistochemistry (IHC) of control and morphologically altered respiratory epithelium. Translational work involved clinical resection material. Collectively, 68 unique serum proteins were identified by 2DE-MALDI-TOF mass spectrometry and 13 reached statistical significance (p?<?0.05). EGF, amphiregulin and the EGFR endosomal sorting protein VPS28 were induced up to 5-fold while IHC confirmed strong induction of these proteins. Furthermore, ApoA1, α-2-macroglobulin, and vitamin-D binding protein were nearly 6- and 2-fold upregulated in AAH; however, ApoA1 was oppositely regulated in LC to evidence disease stage dependent regulation of this tumour suppressor. Conversely, plasminogen and transthyretin were highly significantly repressed by 3- and 20-fold. IHC confirmed induced ApoA1, Fetuin-B and transthyretin expression to influence calcification, inflammation and tumour-infiltrating macrophages. Moreover, serum ApoA4, ApoH and ApoM were 2-, 2- and 6-fold repressed; however tissue ApoM and sphingosine-1-phosphate receptor expression was markedly induced to suggest a critical role of sphingosine-1-phosphate signalling in PL and malignant transformation. Finally, a comparison of three different LC models revealed common and unique serum biomarkers mechanistically linked to EGFR, cMyc and cRaf signalling. Their validation by IHC on clinical resection material established relevance for distinct human lung pathologies. In conclusion, we identified mechanistic biomarker candidates recommended for in-depth clinical evaluation.     

Plasma Protein Biomarkers of Hepatocellular Carcinoma in HCV-Infected Alcoholic Patients with Cirrhosis

Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers in the world, with limited options for treatment unless timely diagnosed. Chronic hepatitis C virus (HCV) infection and persistent heavy alcohol consumption are independent risk factors for HCC development, which may induce a specific protein expression pattern different from those caused separately. The aim of the study was to identify protein biomarkers for the detection of HCC in HCV-infected alcoholic patients with cirrhosis in order to improve survival. We compared protein expression profiles of plasma samples from 52 HCV-infected alcoholic patients with and without HCC, using 2-D DIGE coupled with MALDI-TOF/TOF mass spectrometry. The 2-D DIGE results were analyzed statistically using Decyder software, and verified by western-blot and ELISA. In plasma samples from HCV-infected alcoholic patients, we found significantly differential expression profiles of carboxypeptidase-N, ceruloplasmin (CP), complement component 4a (C4a), fibrinogen-alpha (FGA), immunoglobulin mu chain C region, serum albumin, and serum paraoxonase/arylesterase 1 (PON1). Deregulation of plasma/serum levels of the identified proteins was associated to HCV, ethanol consumption, and/or HCC progression. In the validation through ELISA, C4a serum concentration was increased in HCC patients (2.4±1 ng/mg vs 1.8±0.6 ng/mg; p = 0.029), being the only independent predictor of HCC in the multivariate analysis (OR = 2.15; p = 0.015), with an AUROC = 0.70. The combination of C4a, FGA, CP and PON1 improved slightly the predictive ability of C4a alone (AUROC 0.81). In conclusion, we identified proteins related to acute-phase response, oxidative stress, or immune response, whose differential expression in plasma may be attributed to the presence of HCC. Among them, C4a, and its combination with CP, FGA and PON1, could be considered as potentially reliable biomarkers for the detection of HCC in HCV-infected alcoholic patients.     

用多重PCR检测上海地区汉族人群9个STR基因座的多态性

利用多重PCR和四色荧光（5－FAM,JOE,NED和ROX）自动化检测技术调查上海地区汉族人群D3S1358、vWA、FGA、D8S1179、D21S11、D18S51、D5S818、D13S317、D7S820等9个STR基因座多态性分布并计算 该9个基因座的的基因频率（Pi)、个体鉴别力（DP）、无偏倚期望杂合性（H）、多态性信息含量（PIC）和非父排除概率（PE）。结果显示：9个STR基因座的基因型分布符合Hardy-Weinberg平衡,9个STR基因座中FGA基因座的DP值最高为0.9584,D8S1179的H值最高为0.9403,D18S51的PIC值最高为0.8560,D18S51的PE值最高为0.7391,9个STR基因座累积个体鉴别力（CDP)为0.9999996,累积非父排除能力（CPE）为0.99991。9个STR基因座适合作为中国人群的遗传标志,用于人类学、遗传疾病基因连锁分析、法医学亲子鉴定和个体识别等研究领域。     

用毛细管电泳技术对北京汉族人群9个STR基因座遗传多态性的研究

为对北京汉族D3S1358、vWA、FGA、D8S1179、D21S11、D18S51、D5S818、D13S317及D7S820等9个STR基因座的遗传多态性进行群体遗传学研究,利用荧光标记复合扩增及毛细管电泳自动荧光检测的方法,对236名无关个体获得9个STR基因座等位基因的分布频率,结果均符合Hardy-Weinberg平衡.计算了各基因座的杂合度（H）、个人识别能力（DP）、偶合率（PM）、非父排除率（EPP）和多态性信息总量（PIC）等群体遗传学数据.结果表明,这9个STR基因座多态性好,灵敏度高,可用于人类遗传分析及法医学中的亲子鉴定和个人识别.     

中国北方汉族人群Apolipoprotein基因T-1131C多态与急性冠脉综合征的关联研究

目的:探讨ApoA5基因T-1131C多态性与急性冠脉综合征(acute coronary syndrome,ACS)的相关关系。方法:采用聚合酶链反应-限制性片段长度多态性技术结合琼脂糖凝胶电泳和基因测序等方法对675例ACS的患者和660例正常对照组进行检测,分析ApoA5基因T-1131C单核苷酸多态的基因型和等位基因频率的在ACS组和对照组的分布情况。结果:ApoA5基因T-1131C单核苷酸多态在ACS组和对照组间的分布频率皆符合Hardy-Weinberg平衡定律(P0.05),ApoA5基因T-1131C单核苷酸多态三种基因型(TT型,TC型和CC型)在ACS组分布频率分别为35.4%,48.1%和16.4%,在对照组的分布频率分别为41.1%,48.6%和10.4%。ApoA5基因T-1131C单核苷酸多态的CC等位基因在ACS组和对照组间的分布存在显著性差异(P=0.002),C等位基因是ACS发病的独立的危险因素1.28(P=0.002,95%CI=1.09-1.57)。Logistic回归校正性别、年龄、体重指数、吸烟、高血压、高脂血症、糖尿病等CAD易患因素后,ApoA5基因T-1131C多态与ACS的发病仍存在相关关系。结论:在中国北方汉族人群中ApoA5基因T-1131C多态与ACS的发病相关,ApoA5基因T-1131C多态C等位基因是ACS发病的独立危险因素。     

Variation of plasma protein parameters in four free-ranging reindeer herds and in captive reindeer under defined feeding conditions

Plasma total protein (TP), albumin (ALB) and globulin (GLOB) concentrations and albumin/globulin ratio (A/G) were analysed from blood samples collected from free-ranging reindeer (Rangifer tarandus tarandus) herds at varying times of year. The same parameters were followed in nine captive reindeer with varying protein and energy intake. Variation in the blood constituents of free-ranging reindeer was analysed in relation to different extrinsic and intrinsic factors and compared to findings from captive animals, allowing the analysis of effects of protein and energy intake. There was large overall variation in TP, ALB, GLOB and A/G ratio in the free-ranging animals, ranging between 36-110 g/L, 18-59 g/L, 17-59 g/L and 0.5-2.1. The variation between months and years was significant for all variables except the A/G ratio, where no year effect was noted. Increase in live body mass was associated with a small significant increase and pregnancy with a small significant decrease in all dependent variables, except for the A/G ratio. Age did not have a significant effect on any of the blood constituents when body mass was included in the same model. In captive animals, feeding lichens with low protein content was related to a significant decline in TP, ALB and GLOB, but not in the A/G ratio, whereas feeding commercial ration increased plasma TP, ALB and GLOB significantly. Extrinsic factors such as season and year explained majority of variation in the blood constituents of free-ranging reindeer, whereas body mass, pregnancy and age had only a minor influence. It is concluded that plasma TP and ALB, and to a lesser extent GLOB and A/G ratio may serve as nutritional biomarkers of reindeer.     

Study of individual patterns of blood protein control during simulation of microgravity effects on humans

Blood samples taken from test subjects in a 7-day immersion experiment were assayed for blood proteins belonging to ??l- and ??2-globulin electrophoretic fractions: ??1-antitrypsin (??l-AT), ??1 acidic glycoprotein (??l-AGP), ceruloplasmin (Cer), haptoglobin (Hp), ??2-macroglobulin (??2-M), and apolipoprotein A (ApoA). Immersion was shown to change the concentrations of all proteins studied; in some cases, concentration changes were observed upon the return to the normal state. In general, the set of identified effects corresponded to the pattern characteristic of an acute-phase response. Temporal profiles of ??l-AGP, Cer, ??2-M, Hp, and ApoA in all subjects were of the same type. Differences were detected primarily in the rate and amplitude of the concentration shifts. However, changes in the ??l-AT content during immersion varied in different subjects. Although the ApoA content decreased in all subjects of the study group, in three subjects it dropped below the bottom reference range. In two of them, the baseline ApoA concentrations were also significantly lower compared to the other subjects. The results of this study suggest that monitoring of blood ??l-AT and ApoA in the period of adaptation to altered environmental conditions may be informative for assessment of individual adaptability.     

Generation of killer lymphocytes in vitro against human autologous leukemia cells with leukemic blasts and BCG extract

Summary Acute lymphoblastic leukemia patients under 18 years of age were studied to determine the ability of their remission lymphocytes to kill autologous leukemic blasts (ALB) following in vitro sensitization with their leukemic cells and/or soluble extract of BCG (BCG-SE). Remission lymphocytes, when cultured together with the mitomycin-treated ALB, became significantly lytic for ALB but not for autologous remission lymphocytes. The ALB were usually immunogenic at low concentrations and no cytotoxic lymphocytes were generated at a ratio of 1:1 of responding lymphocytes to stimulating leukemic cells. T-leukemic cells appeared to immunize more effectively than null-cell leukemic cells. In some cases, when ALB alone could not generate killer lymphocytes (KL) the combination of ALB and BCG-SE induced more intense cytotoxicity than was induced by BCG-SE alone. In a few other cases, the addition of BCG-SE to mixed lymphocyte leukemic cell cultures potentiated the immunization of lymphocytes by leukemic cells. Inhibition of cytotoxicity induction was noted in one case when remission lymphocytes were cultured together with ALB and BCG-SE. Leukemic cellssensitized lymphocytes from some cancer patients and normal persons were cytotoxic to several but not all patients' leukemic cells tested. Nylon wool-nonadherent, non-E-rosette-forming, and E-rosette-forming cells became cytotoxic following in vitro stimulation with autologous leukemic cells.     

Association Between Single Nucleotide Polymorphisms of DOT1L Gene and Risk of Knee Osteoarthritis in a Chinese Han Population

To investigate associations between single nucleotide polymorphisms rs12982744 and rs12459350 in the DOT1L gene and knee osteoarthritis (OA) susceptibility in a Chinese Han population. DOT1L rs12982744 and rs12459350 polymorphisms were genotyped in patients with knee OA and age- and sex-matched OA-free controls from a Chinese Han population. A total of 605 patients with knee OA and 615 controls were enrolled in the study. GC and CC genotypes of rs12982744, and variant C, were associated with a significantly increased risk of knee OA. On stratification analysis, the association between the risk of OA and rs12982744 GC heterozygotes compared with GG homozygotes was stronger in females and those aged >65 years. In contrast, the GA and AA genotypes of rs12459350 were not significantly associated with the risk of knee OA, even after further stratification analysis according to age or sex. Our results showed that DOT1L rs12982744 G to C change and variant C genotype may contribute to knee OA risk in a Chinese Han population.     

Identification of proteins adducted by lipid peroxidation products in plasma and modifications of apolipoprotein A1 with a novel biotinylated phospholipid probe

Reactive electrophiles generated by lipid peroxidation are thought to contribute to cardiovascular disease and other oxidative stress-related pathologies by covalently modifying proteins and affecting critical protein functions. The difficulty of capturing and analyzing the relatively small fraction of modified proteins complicates identification of the protein targets of lipid electrophiles. We recently synthesized a biotin-modified linoleoylglycerylphosphatidylcholine probe called PLPBSO ( Tallman et al. Chem. Res. Toxicol. 2007, 20, 227-234 ), which forms typical linoleate oxidation products and covalent adducts with model peptides and proteins. Supplementation of human plasma with PLPBSO followed by free radical oxidation resulted in covalent adduction of PLPBSO to plasma proteins, which were isolated with streptavidin and identified by liquid chromatography-tandem mass spectrometry (LC-MS-MS). Among the most highly modified proteins was apolipoprotein A1 (ApoA1), which is the core component of high density lipoprotein (HDL). ApoA1 phospholipid adduct sites were mapped by LC-MS-MS of tryptic peptides following mild base hydrolysis to release esterified phospholipid adducts. Several carboxylated adducts formed from phospholipid-esterified 9,12-dioxo-10( E)-dodecenoic acid (KODA), 9-hydroxy, 12-oxo-10( E)-dodecenoic acid (HODA), 7-oxoheptanoic acid, 8-oxooctanoic acid, and 9-oxononanoic acid were identified. Free radical oxidations of isolated HDL also generated adducts with 4-hydroxynonenal (HNE) and other noncarboxylated electrophiles, but these were only sporadically identified in the PLPBSO-adducted ApoA1, suggesting a low stoichiometry of modification in the phospholipid-adducted protein. Both phospholipid electrophiles and HNE adducted His162, which resides in an ApoA1 domain involved in the activation of Lecithin-cholesterol acyltransferase and maturation of the HDL particle. ApoA1 lipid electrophile adducts may affect protein functions and provide useful biomarkers for oxidative stress.     

Screening novel biomarkers for metabolic syndrome by profiling human plasma N-glycans in Chinese Han and Croatian populations

N-glycans play an essential role in biological process and are associated with age, gender, and body mass parameters in Caucasian populations, whereas no study has been reported in Chinese populations. To investigate the correlation between N-glycan structures and metabolic syndrome (MetS) components, we conducted a population-based study in 212 Chinese Han individuals. The replication study was performed on 520 unrelated individuals from a Croatian island Kor?ula. The most prominent observation was the consistent positive correlations between different forms of triantennary glycans and negative correlations between glycans containing core-fucose with MetS components including BMI, SBP, DBP, and fasting plasma glucose (FPG) simultaneously. Significant differences in a number of N-glycan traits were also detected between normal and abnormal groups of BMI, BP, and FPG, respectively. In the multivariate analysis, the level of monosialylated glycans (structure loadings = -0.776) was the most correlated with the MetS related risk factors, especially with SBP (structure loadings = 0.907). Results presented here are showing that variations in the composition of the N-glycome in human plasma could represent the alternations of human metabolism and could be potential biomarkers of MetS.     

Mitochondrial DNA Haplogroup Confers Genetic Susceptibility to Nasopharyngeal Carcinoma in Chaoshanese from Guangdong,China

Recent studies have shown association of mtDNA background with cancer development. We analyzed mitochondrial DNA (mtDNA) control region variation of 201 patients with nasopharyngeal carcinoma (NPC) and of 201 normal controls from Chaoshan Han Chinese to discern mtDNA haplogroup effect on the disease onset. Binary logistic regression analysis with adjustment for gender and age revealed that the haplogroup R9 (P = 0.011, OR = 1.91, 95% CI = 1.16–3.16), particularly its sub-haplogroup F1 (P = 0.015, OR = 2.43, 95% CI = 1.18–5.00), were associated significantly with increased NPC risk. These haplogroups were further confirmed to confer high NPC risk in males and/or individuals ≥40 years of age, but not in females or in subjects <40 years old. Our results indicated that mtDNA background confers genetic susceptibility to NPC in Chaoshan Han Chinese, and R9, particularly its sub-haplogroup F1, is a risk factor for NPC.     

中国汉族人群(西安)STR基因扫描与遗传结构

选择9种STR基因位点和Amelogenin基因位点,以测序为基础,研究我国汉族人群STR遗传结构.采用基因自动测序仪建立了10个位点基因分析方法,通过对汉族群体的基因扫描、基因分型和遗传结构分析,获得了STR基因传递特征的大量基因遗传数据,在汉族人群DP为1.05×10-0,EPP为0.9998,为建立我国不同民族STR基因数据库、基因资源研究与保护奠定了基础,为生物考古、基因诊断、性别鉴定、个人识别,司法审判、侦察破案提供有力的科学依据.     

Association Between Single Nucleotide Polymorphisms of Asporin (ASPN) and BMP5 with the Risk of Knee Osteoarthritis in a Chinese Han Population

The aim of this study was to investigate associations between single nucleotide polymorphisms rs13301537 in asporin (ASPN) and rs373444 in the bone morphogenetic protein 5 (BMP5) gene with knee osteoarthritis (OA) susceptibility in a Chinese Han population. ASPN rs13301537 and BMP5 rs373444 polymorphisms were genotyped in patients with knee OA and age- and sex-matched OA-free controls from a Chinese Han population. A total of 510 patients with knee OA and 520 controls were enrolled in the study. CT and CC genotypes of rs13301537, and variant C, were associated with a significantly increased risk of knee OA. On stratification analysis, the association between the risk of OA and rs13301537 CT heterozygotes compared with TT homozygotes was stronger in females and those aged >65 years. In contrast, the CT and CC genotypes of rs373444 in BMP5 were not significantly associated with the risk of knee OA, even after further stratification analysis according to age or sex. Our results showed that ASPN rs13301537 T to C change and variant C genotype may contribute to knee OA risk in a Chinese Han population.