Xue He

Multiple genetic variants are associated with colorectal cancer risk in the Han Chinese population.

Colorectal cancer (CRC) is a major health burden worldwide and is the second-leading cause of cancer-related death in Europe. CRC is a complex disease resulting from a series of genetic and epigenetic changes that lead to a stepwise progression from normal mucosa to dysplasia and finally to carcinoma. In this study, we present genetic association results between 25 tag single-nucleotide polymorphisms and CRC in a case–control study (203 cases, 296 controls) of a Han Chinese population. We found that rs1143634 in the interleukin-1&bgr; (IL1B) gene and rs1800871 in the interleukin-10 (IL10) gene were associated with increased risk for CRC in the Han Chinese. Further haplotype analysis revealed that the ‘GAC’ in the SMAD7 (mothers against decapentaplegic homolog 7) gene was found to increase CRC risk (odds ratio=1.48; 95% confidence interval, 1.09–2.01; P=0.012). Our results, combined with previous studies, suggest that IL10, PSCA, IL1B, and SMAD7 are significantly correlated with CRC susceptibility in the Han Chinese population.

Polymorphisms of the TCF4 gene are associated with the risk of schizophrenia in the Han Chinese

Schizophrenia (SCZ) is a complex and severe mental disorder with highly heritability (80%). Several large genome‐wide association studies have identified that the transcription factor 4 (TCF4) polymorphisms were strongly associated with SCZ. Therefore, the present study was to replicate the potential relationships between the TCF4 polymorphisms and SCZ. Furthermore, the study also investigated whether other variants were associated with SCZ in the Han Chinese. We conducted a case‐control study including 499 patients and 500 healthy controls. Five SNPs were successfully genotyped and evaluated the association with SCZ by using χ2 test and genetic model analysis. We found that the genotype “AG” of rs9320010 and “GA” of rs7235757 decreased SCZ risk (OR = 0.70, 95%CI = 0.50–0.99, P = 0.041; OR = 0.69, 95%CI = 0.49–0.97, P = 0.034, respectively). In the genetic model analysis, we also observed that the allele “A” of rs9320010 and “G” of rs7235757 were inversely related with the risk of SCZ in the dominant model (OR = 0.72, 95%CI = 0.52–0.98, P = 0.039; OR = 0.69, 95%CI = 0.50–0.96, P = 0.025, respectively). Further interaction and stratification analysis suggested that rs1452787 was notably correlated with increased SCZ risk in males (OR = 2.77, 95%CI = 1.43–5.35, P = 0.002). Our study indicated that rs9320010, rs7235757, and rs1452787 were prominently associated with SCZ. Further studies are required to verify our findings and focus on determining the biological functions of the SNPs.

Association of the miR-17-5p variants with susceptibility to cervical cancer in a Chinese population.

MicroRNAs (miRNAs) are key regulators of gene expression; however, the extent to which single nucleotide polymorphisms (SNPs) interfere with miRNA gene regulation and affect cervical cancer (CC) susceptibility remains largely unknown. Here, we systematically analyzed miRNA-related SNPs and their association with CC risk, and performed a case-control study of miR-17-5p SNPs and CC risk in a Chinese population. Sixteen SNPs were genotyped in 247 CC cases and 285 controls. Three were associated with CC risk (p < 0.05): the minor allele (A) of rs217727 in H19 increased risk (OR = 1.53, p = 0.002), while the minor alleles (T) of rs9931702 and (T) of rs9302648 in AKTIP decreased CC risk (p = 0.018, p = 0.014). Analysis of the SNPs after stratification based on CC clinical stage and subtype revealed that rs1048512, rs6659346, rs217727, rs9931702, and rs9302648 were associated with CC risk in clinical stages I-II; rs2862833, rs2732044, rs1030389, and rs1045935 were associated with CC risk in clinical stages III-IV; and rs217727, rs9931702, and rs9302648 were associated with CC risk in squamous carcinomas. These data could serve as a useful resource for understanding the miR-17 function, identification of miRNAs associated with CC, and development of better CC screening strategies.

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

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

Association between regulator of telomere elongation helicase1 (RTEL1) gene and HAPE risk: A case-control study

Abstract High altitude pulmonary edema (HAPE) is a paradigm of pulmonary edema. Mutations in regulator of telomere elongation helicase1 (RTEL1) represent an important contributor to risk for pulmonary fibrosis. However, little information is found about the association between RTEL1 and HAPE risk. The present study was undertaken to tentatively explore the potential relation between single-nucleotide polymorphisms (SNPs) in RTEL1 and HAPE risk in Chinese Han population. A total of 265 HAPE patients and 303 healthy controls were included in our case-control study. Four SNPs in RTEL1 were selected and genotyped using the Sequenom MassARRAY method. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression with adjustment for gender and age. All P values were Bonferroni corrected, and statistical significance was set at P < .0025 (.05/20). In allelic model analysis, we found that the allele “G” of rs6089953 and rs6010621 and the allele “A” of rs2297441 were associated with decreased risk of HAPE. In the genetic model analysis, we found that rs6010621, rs6089953, and rs2297441 were relevant to decreased HAPE risk under dominant model (rs6010621: OR = 0.55; 95% CI = 0.39–0.78; P = .001; rs6089953: OR = 0.68; 95% CI = 0.48–0.96; P = .027; rs2297441: OR = 0.63; 95% CI = 0.45–0.89; P = .008, respectively) and additive model (rs6010621: OR = 0.51; 95% CI = 0.46–0.81; P < .001; rs6089953: OR = 0.72; 95% CI = 0.55–0.95; P = .022; rs2297441: OR = 0.73; 95% CI = 0.57–0.95; P = .019, respectively). SNPs rs6010621 remained significant after Bonferroni correction (P < .0025). In addition, haplotype “GG, GT, AT” of rs6089953-rs6010621 were detected significantly associated with HAPE risk (P < .05), haplotype “GG” remained significant after Bonferroni correction (P < .0025). Our findings provide new evidence for the association between SNPs in RTEL1 and a decreased risk HAPE in the Chinese population. The results need further confirmation.

TERT rs2853676 polymorphisms correlate with glioma prognosis in Chinese population

High rates of recurrence and the lack of effective treatments contribute to the poor prognosis of patients with glioma. There is therefore an urgent need for an easily detectable biomarker to facilitate early detection. In this study, we explored the association between TERT rs2853676 genetic polymorphisms and the prognosis of Chinese glioma patients. A total of 481 glioma patients at the Tangdu Hospital of the Fourth Military Medical University in China were included in this study. The overall survival rates were calculated using the Kaplan-Meier method. Prognostic factors were determined through multivariate Cox regression analysis. The overall survival (OS) rates of one, two, and three years were 31%, 10.3%, and 7.5%, respectively. The progress-free survival (PFS) rates of one, two, and three years were 15.7%, 7.3%, and 4.7%, respectively. The genotype “A/G” of TERT rs2857676 decreased the PFS rate (hazard ratios [HR] = 0.824; P = 0.059). The genotype “A/G (HR = 0.803; 95% CI, 0.656 – 0.982; P = 0.032)” and “A/A + A/G” decreased the recurrence rate compared to the genotype G/G (HR = 0.818; 95% CI, 0.675-0.99; P = 0.040). Our study indicates that TERT rs2853676 polymorphisms correlate with glioma survival and recurrence rates in a Chinese population, which suggests that they could potentially serve as prognostic markers in glioma patients.

The relationship between polymorphisms of XRCC5 genes with astrocytoma prognosis in the Han Chinese population

Background Gliomas are highly malignant with a poor prognosis. Studies have reported that DNA repair genes influence risk for glioma, but its relationship with prognosis is unclear. In this study, we want to explore the relationship between DNA repair genes (XRCC3, XRCC4 and XRCC5) and prognosis of astrocytoma in the Chinese Han population. Materials and Methods 160 astrocytoma cases were recruited in our study. Survival probabilities were estimated by using Kaplan–Meier analysis, and significant differences were analyzed by using the log-rank test. Cox proportional hazards models were used to analyze the associations between genotypes with astrocytoma survival. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using multivariable models. All tests were two-sided and p < 0.05 was considered to be significant. Results The SNP (rs9288516) in XRCC5 (HR: 1.69, 95%CI: 1.04 - 2.77, p = 0.049), surgical approach (HR: 0.61, 95%CI: 0.43 - 0.88, p = 0.003) and chemotherapy (HR: 0.71, 95%CI: 0.50 - 0.99, p = 0.029) were associated with astrocytoma prognosis. Further, the “A/A” genotype of rs9288516 in XRCC5 (HR: 1.67, 95%CI: 1.02 - 2.72, p = 0.042) had significantly outcomes after adjusting for potential confounders, patients with poor tumor differentiation and the coexistence of the unfavorable genotypes. Conclusion These results suggest that polymorphisms of XRCC5 play an important role in astrocytoma prognosis in the Chinese Han population which could be used in the determination of astrocytoma prognosis in clinical researches.

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

High altitude pulmonary edema (HAPE) is a type of pneumonedema that mostly occurs under conditions such as high altitude, rapid ascent and hypoxia, amongst others. The ACYP2 polymorphism is suggested to be associated with mean telomere length, and telomere length is significantly longer at a moderate attitude than at sea‐level or at simulated high attitude. The present study aimed to determine whethher there is any association between ACYP2 polymorphism and the risk of HAPE.

A case-control study of the genetic polymorphism of IL6 and HAPE risk in a Chinese Han population

The role of inflammatory cytokines in High‐altitude pulmonary edema (HAPE) remains unclear. The purpose of this study was to evaluate the role of IL4 and IL6 gene polymorphism in the development of HAPE in Chinese people.

Associations between polymorphisms in the IL-4 gene and renal cell carcinoma in Chinese Han population

Renal cell carcinoma (RCC) is considered to be a kind of cytokine reactive tumor. The research has been suggested that the host immune system can regulate the clinical course of RCC. Therefore, cytokine gene polymorphisms in RCC patients were analyzed was necessary. Our study is purpose to analyzing the interleukin-4(IL-4) polymorphisms associated with RCC risk from Han Chinese population. IL-4 genetic polymorphisms were genotyped using Massarray technology from a total of 291RCC and 463 controls. Unconditional logistic regression analysis was performed to analyze their relationship with risk of RCC. A significant association was found between the rs2243250 “C” allel and decreased risk of RCC (OR=0.75, 95%CI=0.59-0.96, P=0.02). Stratified analysis based on the age, gender, smoking status, drinking status revealed no significant association with RCC in age>55, female, smoking and nodrinking. However, for age<55 group (rs2243250, rs2243267, rs2243270), male group (rs2243250), nonsmoking group (rs2227284), and drinking group (rs2243250, rs2227284, rs2243267, rs2243270) polymorphisms were found obviously associated with RCC. The haplotype analyses showed that the haplotype have a significant decreased risk of RCC in the rs2243250/rs2227284/rs2243267/rs2243270/rs2243283/rs2243289 (CGGACA) (Total, OR=0.73, 95%CI=0.54-0.98, P=0.034; Male, OR=0.59, 95%CI=0.39-0.90, P=0.014). Therefore, the present study suggests that IL-4 may be a candidate gene for assessing the risk of RCC.