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Chen Z.,University of Sichuan | Chen Z.,Bio resource Research and Utilization Joint Key Laboratory of Sichuan and Chongqing | Chen Z.,Sichuan University | Jing Y.,University of Sichuan | And 20 more authors.
PLoS ONE | Year: 2017

Cancer of the cervix is associated with infection by certain types of human papillomavirus (HPV). The gene variants differ in immune responses and oncogenic potential. The E6 and E7 proteins encoded by high-risk HPV play a key role in cellular transformation. HPV-33 and HPV- 58 types are highly prevalent among Chinese women. To study the gene intratypic variations, polymorphisms and positive selections of HPV-33 and HPV-58 E6/E7 in southwest China, HPV-33 (E6, E7: n = 216) and HPV-58 (E6, E7: n = 405) E6 and E7 genes were sequenced and compared to others submitted to GenBank. Phylogenetic trees were constructed by Maximum- likelihood and the Kimura 2-parameters methods by MEGA 6 (Molecular Evolutionary Genetics Analysis version 6.0). The diversity of secondary structure was analyzed by PSIPred software. The selection pressures acting on the E6/E7 genes were estimated by PAML 4.8 (Phylogenetic Analyses by Maximun Likelihood version4.8) software. The positive sites of HPV-33 and HPV-58 E6/E7 were contrasted by ClustalX 2.1. Among 216 HPV-33 E6 sequences, 8 single nucleotide mutations were observed with 6/8 non-synonymous and 2/8 synonymous mutations. The 216 HPV-33 E7 sequences showed 3 single nucleotide mutations that were non-synonymous. The 405 HPV-58 E6 sequences revealed 8 single nucleotide mutations with 4/8 non-synonymous and 4/8 synonymous mutations. Among 405 HPV-58 E7 sequences, 13 single nucleotide mutations were observed with 10/13 non-synonymous mutations and 3/13 synonymous mutations. The selective pressure analysis showed that all HPV- 33 and 4/6 HPV-58 E6/E7 major non-synonymous mutations were sites of positive selection. All variations were observed in sites belonging to major histocompatibility complex and/or Bcell predicted epitopes. K93N and R145 (I/N) were observed in both HPV-33 and HPV-58 E6. © 2017 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Xiong D.-K.,Sichuan University | Xiong D.-K.,Bio resource Research and Utilization Joint Key Laboratory of Sichuan and Chongqing | Xiong D.-K.,Biotechnology Academy of Nanchuan | Chen H.-H.,Sichuan University | And 11 more authors.
Asian Journal of Andrology | Year: 2015

The reported effects of the glutathione S-transferase (GSTs) genes (GSTM1, GSTT1, and GSTP1) on male factor infertility have been inconsistent and even contradictory. Here, we conducted a case-control study to investigate the association between functionally important polymorphisms in GST genes and idiopathic male infertility. The study group consisted of 361 men with idiopathic azoospermia, 118 men with idiopathic oligospermia, and 234 age-matched healthy fertile male controls. Genomic DNA was extracted from the peripheral blood, and analyzed by polymerase chain reaction and restriction fragment length polymorphism analysis. There was a significant association between the GSTP1 variant genotype (Ile/Val + Val/Val) with idiopathic infertility risk (odds ratio [OR]: 1.53; 95% confidence interval [CI]: 1.11-2.11; P = 0.009). Similarly, a higher risk of infertility was noted in individuals carrying a genotype combination of GSTT1-null and GSTP1 (Ile/Val + Val/Val) (OR: 2.17; 95% CI: 1.43-3.31; P = 0.0002). These results suggest an increased risk of the GSTP1 variant genotype (Ile/Val + Val/Val) for developing male factor infertility. Our findings also underrate the significance of the effect of GSTM1 and/or GSTT1 (especially the former) in modulating the risk of male infertility in males from Sichuan, southwest China. © 2015 AJA, SIMM & SJTU. All rights reserved 1008-682X.


Li X.Y.,Sichuan University | Li X.Y.,Bio Resource Research and Utilization Joint Key Laboratory of Sichuan and Chongqing | Li X.Y.,Key Laboratory of Bio Resources and Eco Environment | Ye J.Z.,Sichuan University | And 17 more authors.
Genetics and Molecular Research | Year: 2015

We examined the association between the methionine synthase reductase (MTRR A66G), methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), and methionine synthase (MS A2756G) genotypes and non-obstructive male infertility in a Chinese population. This case-control study included 162 infertile Chinese patients with azoospermia (N = 100) or oligoasthenozoospermia (N = 62) and 120 fertile men as controls. The polymorphisms MTRR A66G, MTHFR C677T, A1298C, and MS A2756G were identified by direct DNA sequencing and the results were statistically analyzed. We found no association between the incidence of any of these variants in azoospermia patients and control populations. The frequency of the MTRR66 polymorphic genotypes (AG, AG+GG) was significantly higher in the oligoasthenozoospermia group compared to the controls (P = 0.013, 0.012). Our findings revealed an association between the single-nucleotide polymorphism A66G in the MTRR gene and male infertility, particularly in oligoasthenozoospermia males, suggesting that this polymorphism is a genetic risk factor for male infertility in Chinese men. © FUNPEC-RP.


Zhang X.,Sichuan University | Zhang X.,Bio Resource Research and Utilization Joint Key Laboratory of Sichuan and Chongqing | Zhang X.,Key Laboratory of Bio Resources and Eco Environment | Ding M.,Sichuan University | And 11 more authors.
Systems Biology in Reproductive Medicine | Year: 2015

Four genes involved in DNA double-strand break repair and chromosome synapsis, i.e., testis expressed gene 11 (TEX11), testis expressed gene 15 (TEX15), mutL homolog 1 (MLH1), and homolog 3 (MLH3), play critical roles in genome integrity, meiotic recombination, and gametogenesis. We explored the possible association between single nucleotide polymorphisms (SNPs) in these genes and idiopathic male infertility involving azoospermia or oligozoospermia. A total of 614 fertile control and infertile men were recruited to this study in Sichuan, China. The latter group included 244 men with azoospermia and 72 men with oligozoospermia. Six SNPs in the TEX11, TEX15, MLH1, and MLH3 genes were investigated in both patients and controls by sequencing. The frequency distributions of SNPs rs6525433, rs175080, rs6525433-rs4844247, and rs1800734-rs175080 were found to be significantly different between patients and control groups (p<0.05), while rs4844247, rs323344, rs323346, and rs1800734 showed no significant difference between the two cohorts. Thus, the SNPs TEX11 rs6525433, MLH3 rs175080, rs6525433-rs4844247, and rs1800734-rs175080 might be associated with male infertility. © 2015 Informa Healthcare USA, Inc. All rights reserved.


Ren H.Y.,Sichuan University | Ren H.Y.,Bio Resource Research and Utilization Joint Key Laboratory of Sichuan and Chongqing | Ren H.Y.,University of Sichuan | Zhong R.,Sichuan University | And 11 more authors.
Genetics and Molecular Research | Year: 2015

Previous studies have shown that genetic polymorphisms in exon7 of the NSUN7 gene can be used as an infertility marker in Iranian men with asthenospermia. However, there have been no equivalent studies in China. In the present study, we investigated the possible association between the genetic polymorphisms in exon7 of NSUN7 and asthenospermia in a Chinese Han population. We recruited 240 asthenospermic men as a patient group and 256 normospermic men as a control group, and analyzed the semen parameters on the basis of World Health Organization (WHO) guidelines. The genetic polymorphisms in exon7 of NSUN7 were detected by DNA sequence analysis. The results were analyzed statistically and a P value < 0.05 was considered significant. There were two genetic polymorphisms, c.906C>T and c.922T>G, in exon7 of NSUN7. We found relatively similar genotypes and allele frequencies between the two groups (P = 0.928, P = 0.928, respectively). The combined genotypes of the two polymorphisms did not identify a haplotype associated with asthenospermia (P = 0.824, P = 0.824, respectively). Our findings revealed that genetic polymorphisms in exon7 of the NSUN7 gene are not associated with asthenospermia in Chinese Han men. © FUNPEC-RP.


Chen Z.,University of Sichuan | Chen Z.,Bio resource Research and Utilization Joint Key Laboratory of Sichuan and Chongqing | Chen Z.,Sichuan University | Jing Y.,University of Sichuan | And 20 more authors.
Virology Journal | Year: 2016

Background: Cervical cancer is associated with infection by certain subtypes of human papillomavirus (HPV). The L1 protein comprising HPV vaccine formulations elicits high-titre neutralizing antibodies and confers protection against specific HPV subtypes. HPV L2 protein is an attractive candidate for cross-protective vaccines. HPV-33 and HPV-58 are very prevalent among Chinese women. Methods: To study the gene intratypic variations and polymorphisms of HPV-33 and HPV-58 L1/L2 in Sichuan China, HPV-33 and HPV-58 L1 and L2 genes were sequenced and compared with other genes submitted to GenBank. Phylogenetic trees were constructed by maximum-likelihood and the Kimura 2-parameters methods (MEGA 6). The secondary structure was analyzed by PSIPred software, and HPV-33 and HPV-58 L1 homology models were created by SWISS-MODEL software. The selection pressures acting on the L1/L2 genes were estimated by PAML 4.8. Results: Among 124 HPV-33 L1 sequences 20 single nucleotide mutations were observed included 8/20 non-synonymous and 12/20 synonymous mutations. The 101 HPV-33 L2 sequences included 12 single nucleotide mutations comprising 7/12 non-synonymous and 5/12 synonymous mutations. The 223 HPV-58 L1 sequences included 32 single nucleotide mutations comprising 9/32 non-synonymous and 23/32 synonymous mutations. The 201 HPV-58 L2 sequences comprised 26 single nucleotide mutations including 9/26 non-synonymous and 17/26 synonymous mutations. Selective pressure analysis showed that most of the common non-synonymous mutations showed a positive selection. HPV-33 and HPV-58 L2 were more stable than HPV-33 and HPV-58 L1. Conclusions: HPV-33 and HPV-58 L2 were better candidates as clinical diagnostic targets compared with HPV-33 and HPV-58 L1. Clinical diagnostic probes and second-generation polyvalent vaccines should be designed on the basis of the unique sequence of HPV-33 and 58 L1/L2 variations in Sichuan, to improve the accuracy of clinical detection and the protective efficiency of vaccines. © 2016 The Author(s).


Zhang Y.,University of Sichuan | Zhang Y.,Bio resource Research and Utilization Joint Key Laboratory of Sichuan and Chongqing | Cao M.,University of Sichuan | Cao M.,Bio resource Research and Utilization Joint Key Laboratory of Sichuan and Chongqing | And 12 more authors.
Gene | Year: 2016

Human papillomavirus (HPV) is the major causative agent of cervical cancer, which accounts for the second highest cancer burden in women worldwide. HPV-52, the prevalent subtype in Asia, especially in southwest China, was analyzed in this study. To analyze polymorphisms, intratypic variants, and genetic variability in the E6-E7 (n = 26) and L1 (n = 53) genes of HPV-52, these genes were sequenced and the sequences were submitted to GenBank. Phylogenetic trees were constructed using the neighbor-joining and Kimura 2-parameters methods, followed by analysis of the diversity of secondary structure. Finally, we estimated the selection pressures acting on the E6-E7 and L1 genes. Fifty-one novel variants of HPV-52 L1, and two novel variants of HPV-52 E6-E7 were identified in this study. Thirty single nucleotide changes were observed in HPV-52 E6-E7 sequences with 19/30 non-synonymous mutations and 11/30 synonymous mutations (five in the alpha helix and five in the beta sheet). Fifty-five single nucleotide changes were observed in HPV-52 L1 sequences with 17/55 non-synonymous mutations (seven in the alpha helix and fourteen in the beta sheet) and 38/55 synonymous mutations. Selective pressure analysis predicted that most of these mutations reflect positive selection. Identifying new variants in HPV-52 may inform the rational design of new vaccines specifically for women in southwest China. Knowledge of genetic variation in HPV may be useful as an epidemiologic correlate of cervical cancer risk, or may even provide critical information for developing diagnostic probes. © 2016 Elsevier B.V.

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