A Functional Variant rs2072915 is Associated with the Susceptibility and Mortality of Cervical Squamous Cell Carcinoma.

PURPOSE: Genetic variant has been demonstrated to be a risk factor for the occurrence and outcome of cervical squamous cell carcinoma (CSCC). From previous genome wide association studies, 6p21.32 has been identified as a susceptibility locus of CSCC. The purpose of this study was to investigate the association of a polymorphism rs2072915 located in 6p21.32 with the risk of CSCC and examine the potential mechanism of the rs2072915 in CSCC pathogenesis. PATIENTS AND METHODS: The rs2072915 was genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism. miR-637 and RXRB mRNA expression levels in CSCC patients were examined using quantitative PCR. miR-637 target site was determined using the dual-luciferase reporter assay. RESULTS: The rs2072915 was associated with a significantly increased risk (AA vs TT: adjusted OR = 2.48, 95% CI, 1.57-3.94, P < 0.001; AT/AA vs TT: adjusted OR = 1.38, 95% CI, 1.06-1.80, P = 0.018; A vs T: adjusted OR = 1.49, 95% CI, 1.21-1.84, P < 0.001, respectively) and shorter survival time of CSCC (P = 0.03). Patients with the rs2072915 AA genotype displayed lower levels of RXRB that is a target of miR-637. CONCLUSION: These findings suggest that the rs2072915 T > A change might augment the binding energy of miR-637 to RXRB, result in lower levels of RXRB, and thus contribute to the risk of CSCC.

[Association of coagulation factor V gene polymorphism with unexplained recurrent spontaneous abortion among ethnic Hans from Wenzhou area].

OBJECTIVE: To assess the association of coagulation factor V gene polymorphisms with unexplained recurrent spontaneous abortion (URSA) among ethnic Han Chinese from Wenzhou area. METHODS: Ninety-six patients with URSA and 103 females with a history of normal pregnancy were recruited. Genotypes of coagulation factor V gene were determined through target sequence capture and high-throughput sequencing. The results were confirmed with a MassARRAY system. Allelic and genotypic frequencies between the two groups were compared. RESULTS: Nineteen single nucleotide polymorphism (SNPs), except coagulation factor V Leiden, were identified in the two groups. The frequencies of rs9287090 allele A, rs1046712 allele T and rs1800594 allele G of the URSA group were lower than those of the control group (6.77% vs. 16.50%, 3.12% vs. 13.11%, 10.94% vs. 18.45%, respectively). After Bonferroni and false discovery rate correction, rs9287090 and rs1046712 were significantly associated with URSA (corrected P<0.05). Although genotypic distribution of rs9287090 and rs1046712 also differed between the two groups, the corrected P value showed no significance (corrected P>0.05). A complete linkage disequilibrium (r2=1, D'=1) of rs6022 and rs6029 was observed for the haplotype block rs6022-rs6029-rs6028. The frequencies of rs6022 allele A and rs6029 allele T were higher in the URSA group with corrected insignificance (75.00% vs. 65.53%, corrected P>0.05). Furthermore, significantly more A-T-T haplotype was found in the URSA group (75.00% vs. 65.50%, OR=1.578, 95%CI:1.021-2.438, χ2=4.248, P<0.05). CONCLUSION: The decreased rate of rs9287090 allele A, rs1046712 allele T, and rs1800594 allele G may contribute to the susceptibility to URSA among ethnic Han Chinese from Wenzhou area. The rs6022 allele A and rs6029 allele T may also predispose to URSA.

Clinical features and genetic diagnosis of hereditary spinocerebellar ataxia 3.

Spinocerebellar ataxia type 3 (SCA3) is a rare inherited autosomal dominant progressive neurological disorder, which results from a CAG­repeat expansion in the gene encoding the deubiquitinating enzyme, ataxin­3. At present, no effective treatment is available for this fatal disorder; however, certain studies have suggested that reducing the levels of mutant ataxin­3 protein may reverse or halt the progression of disease in patients with SCA3. In the present study, clinical examinations were performed on a patient with SCA3 who exhibited disease features including coughing, expectoration and was bedridden with mobility limitation. CAG repetitions at SCA­associated genes were detected in the patient's family by performing standard polymerase chain reaction (PCR) and triple­repeat primed PCR. The numbers of CAG­repeats within the two alleles of the gene of interest in the patient were 15 and 78. Notably, the patient's brother, who harbored 76 CAG­repeats in one allele of the gene of interest, did not exhibit severe disease symptoms. These results suggest that the number of CAG­repeats is a critical for determination of SCA3 disease severity and time of onset. In addition, the defined phenotypic characteristics of the patient in the present study provide useful insight for more accurate clinical diagnosis and genotyping of future patients.

[Analysis of the association of human leukocyte antigen DQ gene polymorphisms with unexplained recurrent spontaneous abortion among ethnic Han Chinese from Wenzhou region].

OBJECTIVE: To assess the association of human leukocyte antigen DQ gene polymorphisms with unexplained recurrent spontaneous abortion (URSA) among ethnic Han Chinese from Wenzhou region. METHODS: Fifty couples with URSA (URSA group) and 66 couples with normal pregnancy history (control group) were recruited. The alleles of HLA-DQA1 and HLA-DQB1 were analyzed by polymerase chain reaction with specific sequence primers (PCR-SSP) in all subjects. The frequency distribution of HLA-DQ alleles, odds ratios (OR) between each group and sharing of HLA-DQ alleles were calculated. RESULTS: The frequency distribution of HLA-DQB1*03:03 allele in the females with URSA was significantly higher than that healthy females (21.00% vs. 9.85%, OR=2.433, 95%CI: 1.232-4.894, χ(2)=5.657, P<0.05). The HLA-DQB1*05:03 allele was present among the healthy females with a frequency of 3.03%, and was not detected among females with URSA. For both males and females, the HLA-DQB1*05:02 allele were only typed in control group with frequencies of 6.06% and 5.30%, respectively. The sharing of HLA-DQA1 alleles in couples with URSA was increased compared with the control group (70.27% vs. 44.64%, OR=2.931, 95%CI: 1.216-7.067, P<0.05). CONCLUSION: The increased sharing of HLA-DQA1 alleles may contribute to the susceptibility of URSA among ethnic Han Chinese from Wenzhou region. The allele of HLA-DQB1*03:03 in the females may be predisposing factor for URSA. However, the HLA-DQB1*05:02 allele in both gender and HLA-DQB1*05:03 allele in females may confer a protective effect.

[Dynamic change of plasma prethrombotic state molecular marker levels in perioperative period of patients and its clinical significance].

This study was aimed to investigate the dynamic changes of plasma prethrombotic state molecular marker levels during perioperation of patients and to provide laboratorial evidence for clinical diagnosis of these patients so as to take intervenient measure to high risk patients. 40 patients with gynecological and urological malignant tumors (without metastasis) and 20 patients with benign tumors and 20 healthy individuals were selected for analysis. The levels of plasm prethrombotic state molecular markers including TF, TFPI, TpP, PAI-1, P-S, TAT and D-D were measured by using ELISA method and transmission immunity nephelometry. The results showed that the levels of TF, TpP, D-D, P-S and TAT in plasma of patients with malignant tumors at 6 hours after operation were higher than that before operation, but the levels of TFPI and PAI-1 in these patients after operation were lower than before operation, and there was significant difference as compared with the levels of these markers before operation. At day 3 after operation, the levels of TF, TpP and D-D continuously increased; the level of PAI-1 begins to elevate, there were significant difference in comparison with that before operation; the levels of P-S and TAT decreased, but still were higher than that before operation. At day 7 after operation, the levels of TpP, TAT, P-S, TFPI and PAI-1 returned to levels before operation, but the levels of TF and D-D were still higher than that before operation, and showed significant difference from that before operation. In patients with benign tumors and non-operation patients, the levels of prethrombotic state molecular markers mentioned above at different points of time after operation did not present difference, except levels of TF and D-D that at 6 hours after operation were higher than that before operation. It is concluded that at 6 hours after operation of patients with gynecological and urological malignant tumours, the plasma levels of prethrombotic state molecular markers are in higher state of coagulation and fibrinolysis, at 3 days after operation these levels are mainly in coagulation state. At 7 days after operation, the level of these markers returned to levels before operation. At 6 hours after operation the levels of these markers in patients with benign tumors are in mild coagulation state.