Background: Hepatocellular carcinoma (HCC) is a common fatal malignant tumor worldwide. Signal transducer and activator of transcription 4 (STAT4) is HCC susceptibility gene identified by genome-wide association study. The purpose of the present study was to determine the association between four candidate single nucleotide polymorphisms (SNPs) in STAT4 genes and HCC risk in Chinese Han population. Methods: A case–control study was conducted to assess the association between STAT4 SNPs and HCC risk in 1011 Chinese Han population. Agena MassARRAY was used to genotype SNPs. The association between SNPs and HCC susceptibility under different genetic models was evaluated by logistic regression analysis. Multifactorial dimension reduction (MDR) analyzed the interaction of ‘SNP–SNP’ in HCC risk. The difference of clinical characteristics between different genotypes was completed by ANOVA. Results: The results showed that STAT4 rs11889341 was significantly associated with HCC risk under multiple genetic models (homozygote: odds ratio (OR) = 0.60, P =0.033; recessive: OR = 0.63, P =0.028; log-additive: OR = 0.83, P =0.032). The results of subgroup analysis showed that STAT4 rs11889341 is significantly associated with HCC risk with participants who were >55 years, male or smoking. Both STAT4 rs7574865 and rs10174238 were significantly associated with HCC risk among participants who were >55 years, smoking or drinking. STAT4 haplotype (T rs11889341 T rs7574865 ) could reduce the risk of HCC. In addition, rs11889341 and rs7574865 were significantly associated with the level of serum ferritin (SF). Conclusion: STAT4 rs11889341, rs7574865 or rs10174238 is potentially associated with HCC risk in Chinese Han population. In particular, rs11889341 showed outstanding association with HCC risk.

Objective: To determine the levels of s-IgA in saliva of caries patients and healthy controls, and to evaluate whether there is a correlation between it and caries by meta-analysis. Methods: The PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library, Scopus, Chinese National Knowledge Infrastructure, Wanfang Data, Chongqing VIP database for Chinese Technical Periodicals, and China BioMedical Literature Services System databases were searched initially in April 2020 and repeated in August 2020. Two independent evaluators screened the literature and extracted the data according to the inclusion and exclusion criteria. R 4.0.2 software was used for meta-analysis. I 2 test was commonly reflected the heterogeneity. Subgroup analysis and meta-regression analysis explore the sources of heterogeneity. Sensitivity analysis, funnel diagram, Begg’s rank correlation, and Egger’s linear regression were used to determine the possibility of publication bias. Results: The study was reviewed according to the project guidelines for optimal reporting (PRISMA) based on meta-analysis. A total of 30 case–control studies were included, with a total sample size of 1545 patients, including 918 caries patients and 627 healthy controls. Salivary s-IgA levels in caries patients were significantly lower than those in healthy controls (SMD = −0.49, 95%CI: [−0.94; −0.03], P =0.03). In addition, the results of subgroup analysis showed that the significant decrease of salivary s-IgA level was correlated with children patients, mixed dentition and Asian people (children: SMD = −0.45, 95%CI: [−0.89; −0.01], P =0.04; mixed dentition: SMD = −0.61, 95%CI: [−1.24; 0.03], P =0.06; Asian: SMD = −0.62, 95%CI: [−1.17; −0.08], P =0.02). The funnel diagram included in the study was symmetrically distributed, and the sensitivity analysis confirmed the robustness of the results. Conclusion: Salivary s-IgA levels in caries patients were significantly lower than in healthy controls. It has also been demonstrated that salivary s-IgA may be used as an alternative measure to identify subjects at risk of caries susceptibility, suggesting that salivary s-IgA may be a protective factor for dental caries.

Background: Gastric cancer (GC) is a complex multifactorial disease. Previous studies have revealed genetic variations associated with the risk of gastric cancer. The purpose of the present study was to determine the correlation between single-nucleotide polymorphisms (SNPs) of ZBTB20 and the risk of gastric cancer in Chinese Han population. Methods: We conducted a ‘case–control’ study involving 509 GC patients and 507 healthy individuals. We selected four SNPs of ZBTB20 (10934270 T/C, rs9288999 G/A, rs9841504 G/C and rs73230612 C/T), and used logistic regression to analyze the relationship between those SNPs and GC risk under different genetic models; multi-factor dimensionality reduction (MDR) was used to analyze the interaction of “SNP–SNP” in gastric cancer risk; ANOVA and univariate analysis were used to analyze the differences in clinical characteristics among different genotypes. Results: Our results showed that ZBTB20 rs9288999 is a protective factor for the risk of gastric cancer in multiple genetic models, of which the homozygous model is the most significant (OR = 0.48, P =0.0003); we also found that rs9288999 showed a significant correlation with reducing the risk of gastric cancer in different subgroups (BMI; age; gender; smoking or drinking status; adenocarcinoma); rs9841504 is associated with increased GC risk in the participants with BMI>24 kg/m 2 ; rs9841504 and rs73230612 are certainly associated with clinical characteristics of platelet and carbohydrate antigen 242, respectively. Conclusion: Our results suggest that ZBTB20 rs9288999 may be important for reducing the risk of GC in the Chinese Han population.

Numerous evidence has revealed that single-nucleotide polymorphisms (SNPs) are associated with liver cancer risk. To assess whether the MIR17HG polymorphisms are associated with the liver cancer risk in the Chinese Han population, we performed a case–control (432 liver cancer patients and 430 healthy controls) study. Genotyping of four variants of MIR17HG was performed with the Agena MassARRAY platform. We used χ 2 test to compare the distribution of SNPs allele and genotypes frequencies of cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis to evaluate the association under genetic models. The results indicated that the rs7318578 was significantly associated with increased the risk of liver cancer in the allele (OR = 1.45, 95% CI: 1.18–1.77, P =3.04E-04), recessive (OR = 3.69, 95% CI: 2.45–5.56, P =4.52E-10) and additive model (OR = 1.35, 95% CI: 1.13–1.62, P =0.001). Moreover, we found that individuals with the genotype CC of rs7318578 presented with an increased risk of liver cancer (OR = 3.03, 95% CI: 1.98–4.65, P =3.83E-07); however, the CA genotype of rs7318578 significantly decreased the risk of liver cancer (OR = 0.61, 95% CI: 0.45–0.83, P =0.001, compared with those with the AA genotype. Our findings indicated that MIR17HG polymorphism (rs7318578) contributes to liver cancer susceptibility to the Chinese Han population. Further studies with larger samples are required to confirm the results, as well as functional studies to determine the role of this SNP in miRNA expression or molecular pathways.

The Gremlin-2 (GREM2) plays crucial roles in modulating bone homeostasis through the bone morphogenetic protein-2 pathway. However, GREM2 gene variants in osteoporosis were less frequent in a Chinese population. Therefore, the present study recruited 310 patients with osteoporosis and 339 healthy postmenopausal women to assess the correlation of GREM2 gene polymorphisms with the risk of osteoporosis. Polymerase chain reaction (PCR) and Sanger sequencing were utilized to genotype samples. The results showed that GREM2 gene rs4454537, not rs11588607, polymorphism was significantly associated with an increased risk of osteoporosis in postmenopausal women. Moreover, stratified analyses indicated a significant association between rs4454537 polymorphisms and body mass index of <25 kg/m 2 . Additionally, the association between GREM2 rs4454537 polymorphism and clinical characteristics was assessed, which showed that this locus decreased the bone mineral density (BMD) in postmenopausal osteoporotic individuals. Furthermore, individuals with CC genotype appeared to have a higher GREM2 expression compared with those bearing the TT genotype of rs4454537 polymorphism. However, the genotype distribution of rs4454537 polymorphism showed no statistical difference between osteoporotic patients as a function of fracture status. In summary, GREM2 rs4454537 polymorphism decreases BMD and increases osteoporotic risk in postmenopausal women.

Interleukin (IL)-17 have been reported to be associated with the pathogenesis of colorectal cancer (CRC). Few studies investigated the association between IL-17 gene polymorphisms and risk of CRC with inconsistent findings. Thus, we recruited 352 CRC cases and 433 controls in a Chinese population and their genotyping was done using polymerase chain reaction-restriction fragment length polymorphism method. Our data showed that IL-17A rs2275913 polymorphism was associated with the increased risk of CRC, while no association was observed for IL-17F rs763780 polymorphism. Stratified analyses revealed that the significant association was also obtained in the females, smokers, drinkers and age ≥ 60 years groups for rs2275913 polymorphism. Moreover, the CC and/or GC genotype of rs2275913 polymorphism were correlated with TNM stage and lymph node metastasis. No association was shown between IL-17F rs763780 polymorphism and clinical characteristics of CRC. In conclusion, our data indicate that IL-17A rs2275913 polymorphism but not IL-17F rs763780 polymorphism contributes to increased risk for CRC patients in this Chinese population.

Transforming growth factor (TGF)-β1 contributed to angiotensin II (Ang II)-mediated collagen accumulation after myocardial infarction (MI). The present study aimed to investigate the association of genetic variant of TGF-β1 gene with the risk of MI. The present study recruited a total of 530 MI patients and 651 healthy controls. The genomic DNA was extracted and subjected into polymerase chain reaction (PCR) and Sanger sequencing. The present study indicated that TGF-β1 -913G/C polymorphism was associated with increased risk for MI under the co-dominant, dominant and allelic models. The increased risk effect was also evident among the females, younger subjects (age < 60 years), smokers, non-drinkers and individuals with hypertension. Additionally, the present study observed significant differences among cases and controls in terms of total cholesterol (TC). In conclusion, TGF-β1 -913G/C polymorphism is associated with increased risk for MI. TGF-β1 -913G/C polymorphism may be a potential prognostic biomarker for MI.

Epidermal Growth factor (EGF) could induce colorectal cancer (CRC) cell to develop epithelial mesenchymal-transition and enhance their ability to invade and migrate. Several studies have thrown light on the association between EGF gene polymorphism and risk of CRC, but with conflicting results. Therefore, we determined EGF A61G polymorphism by using PCR-restriction fragment length polymorphism method in 341 CRC cases and 472 controls in a Chinese population. Our results showed that EGF A61G polymorphism increased the risk of CRC in a Chinese population (GG vs AA: adjusted OR: 1.92; 95% CI: 1.27–2.91; P =0.002; GG+AG vs AA: adjusted OR: 1.43; 95% CI: 1.05–1.94; P =0.022; GG vs AG+AA: adjusted OR: 1.65; 95% CI: 1.15–2.39, P =0.007; G vs A: OR: 1.39; 95% CI: 1.14–1.69, P =0.001). Stratified analyses revealed that the significant association was more evident in the females, smokers, drinkers, and old subjects (age ≥60 years). Furthermore, the GG and/or AG genotype carriers were more likely to have larger tumor size and lymph node metastasis. In conclusion, EGF A61G polymorphism is a genetic contributor to CRC in a Chinese Han population.

The levels of cytokines, inflammatory cells, and angiogenic factors increase following diabetic retinopathy (DR), and the association between interleukin-10 (IL-10) gene rs1800896 polymorphism (IL-10 -1082G/A polymorphism) and DR in different populations has been extensively studied. However, the findings are conflicting, and there is no relevant research in Chinese subjects. Therefore, this case–control study involving 327 cases (type 2 diabetes patients with proliferative DR (PDR)) and 461 controls (type 2 diabetes patients without DR) was conducted to address the relationship between IL-10 gene rs1800896 polymorphism and risk of PDR in Chinese population. Genotyping was performed using PCR-based restriction fragment length polymorphism (PCR-RFLP) assay. It was found that GG genotype or G allele of the IL-10 gene rs1800896 polymorphism was associated with decreased risk for PDR. In conclusion, IL-10 gene rs1800896 polymorphism decreases the risk of PDR.

Osteoarthritis (OA) is a degenerative joint disease characterized by joint destruction with cartilage loss and occasional gross derangement of joint integrity. In recent years, several studies have reported the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and knee OA. However, the results were conflicting. To determine the association between ACE gene I/D polymorphism and knee OA, we conducted a hospital-based case–control study with 282 knee OA cases and 316 controls to investigate the association between ACE gene I/D polymorphism and knee OA susceptibility in a Chinese Han population. The present study found that DD genotype or D allele carriers of ACE gene I/D polymorphism increased the risk of knee OA. Stratification analyses of sex, age, and body mass index (BMI) showed significant associations amongst the groups of females, ≥55 years, and abnormal BMI. In addition, the present study made analysis between ACE I/D polymorphism and some clinical features of OA, and found DD genotype of I/D polymorphism was associated with arthralgia. Furthermore, we undertook a meta-analysis together with the present study between this single nucleotide polymorphism (SNP) and knee OA risk. This meta-analysis found that ACE gene I/D polymorphism was associated with increased risk for OA. Stratification analysis of ethnicity in this meta-analysis indicated that I/D polymorphism increased the risk of knee OA amongst the Asians and Caucasians. In conclusion, this case–control study and meta-analysis suggest that ACE gene I/D polymorphism is associated with increased risk for knee OA.

Hypoxia-inducible factors (HIFs) play a crucial role in cancer progression. Several epidemiological studies have demonstrated that HIFs polymorphisms can influence the susceptibility of multiple cancers. However, the relationship of HIFs polymorphisms (rs11549467 and rs17039192) and breast cancer (BC) risk was still unknown. Thus, we performed a case-control study based on 560 BC patients and 583 healthy controls to explore the association between them. Our results indicated a boardline connection between HIF-1 rs11549467 and BC risk (AG compared with GG: OR = 1.61, 95% CI = 1.05–2.49, P =0.03; AG + AA compared with GG: OR = 1.64, 95% CI = 1.08–2.51, P =0.02; AG compared with GG + AA: OR = 1.61, 95% CI = 1.04–2.48, P =0.03; OR = 1.64, 95% CI = 1.09–2.45, P =0.02), while HIF-2 rs17039192 had no influence on breast cancer. Considered the comparison of sample size and potential heterogeneity of previous case–control studies, we concluded that HIF-1 rs11549467 has a marginal effect on BC risk. Further well-designed studies with larger sample size were required.

Tumor necrosis factor superfamily member 4 (TNFSF4), also known as Ox40 ligand (Ox40l), plays an important role in atherosclerosis development. Several studies reported the association between the rs3850641 polymorphism of the TNFSF4 gene and the risk of myocardial infarction (MI). However, the results are inconsistent. In order to explore the relationship between the rs3850641 polymorphism of the TNFSF4 gene and MI, we conducted a case–control study including 454 cases and 512 controls in a Chinese Han population. Genotyping was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The present study found that AA genotype (AA vs. GG: odds ratio (OR) & 95% confidence interval (CI), 2.00(1.04,3.86), P =0.039; AA vs. AG+GG: OR & 95% CI, 1.93(1.00,3.70), P =0.049) or A allele carriers (A vs. G: OR & 95% CI, 1.27(1.00,1.60), P =0.047) of the rs3850641 polymorphism of the TNFSF4 gene increased the risk of MI. In conclusion, this case–control study confirms that the rs3850641 polymorphism of the TNFSF4 gene increases the risk of MI.

Nucleotide excision repair (NER), the core mechanism of DNA repair pathway, was commonly used to maintain genomic stability and prevent tumorigenesis. Previous investigations have demonstrated that single nucleotide polymorphisms (SNPs) of NER pathway genes were associated with various types of cancer. However, there was no research elucidating the genetic association of entire NER pathway with ovarian cancer susceptibility. Therefore, we conducted genotyping for 17 SNPs of six NER core genes ( XPA, XPC, XPG, ERCC1, ERCC2 , and ERCC4 ) in 89 ovarian cancer cases and 356 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of association. The result showed that both ERCC1 rs11615 and XPC rs2228000 were significantly associated with reduced risk of ovarian cancer under dominant genetic model (adjusted OR = 0.35, 95% CI = 0.20–0.61, P =0.0002 and adjusted OR = 0.49, 95% CI = 0.30–0.81, P =0.005 respectively). In addition, XPC rs2228001 and ERCC2 rs238406 had statistically significant association with the increased risk of ovarian cancer under dominant genetic model (adjusted OR = 1.72, 95% CI = 1.02–2.92, P =0.043 and adjusted OR = 2.07, 95% CI = 1.07–4.01, P =0.032 respectively). ERCC1 rs3212986 were related with the increased risk of ovarian cancer under recessive model (adjusted OR = 2.40, 95% CI = 1.30–4.44, P =0.005). In conclusion, our results indicated that ERCC1, XPC and ERCC2 might influence ovarian cancer susceptibility. Further research with large sample size is warranted to validate the reliability and accuracy of our results.