CA Genotype Research Articles

The Association Between GC Gene Polymorphisms and Metabolic Syndrome in Chinese Rural Population: A Case-Control Study.

BackgroundGC (group-specific component globulin) encoding VDBP (Vitamin D binding protein) polymorphisms have been associated with susceptibility to some diseases such as diabetes, obesity, osteoporosis, and polycystic ovary syndrome, but the evidence for metabolic syndrome (MetS) in the Chinese rural population is inconclusive. Therefore, we investigated the relationship between GC variants (rs7041, rs4588, rs2282679, and rs705117) and MetS risk as well as VDBP levels in the Chinese rural population.Patients and MethodsThe participants (range of age: 20–90 years) of this case–control study were recruited from the northern Chinese Han rural population. We matched 445 MetS cases with non-MetS controls in a 1:1 ratio by sex, age (within 5 years). Real-time PCR technology was carried out by TaqMan assays to examine the four variants of rs7041, rs4588, rs2282679, and rs705117 within the GC gene. To identify the association of GC gene polymorphisms with MetS, we calculated ORs using a conditional logistic regression model adjusted for potential confounding factors.ResultsWe observed inverse associations of CA and AA genotypes of rs4588 with risk of MetS (OR = 0.678, 95% CI 0.505–0.910, P = 0.010; 0.603, 95% CI 0.373–0.973, P = 0.039, respectively) compared with carriers of CC genotype. A similar relationship was also found between rs2282679 and MetS, showing that carrying AC genotype of rs2282679 can decrease the risk of MetS (OR = 0.683, 95% CI 0.509–0.917, P = 0.011) compared with carriers of AA genotype. The results of correlation analysis between MetS components and GC polymorphisms showed that the ORs of AA genotype of rs4588 with high level of TG (triglycerides) and low level of HDL-C (high-density lipoprotein cholesterol) were 0.473 (95% CI 0.245–0.911, P = 0.025) and 0.268 (95% CI 0.117–0.615, P = 0.002), respectively; the ORs of CC genotype of rs2282679 with high level of TG and low level of HDL-C were 0.428 (95% CI 0.217–0.842, P = 0.014) and 0.263 (95% CI 0.110–0.628, P = 0.003), respectively. However, there was no significant association between the concentration of VDBP and MetS risk.ConclusionAmong the Chinese rural population, GC polymorphism was associated with lower metabolic syndrome susceptibility, which might be through affecting blood lipid levels (TG and HDL-C).

Studying the genotype of Aryl Hydrocarbon Receptor-Interacting Protein (AIP) Gene (rs641081C>A) in ‎Iraqi Samples with Acromegaly Pituitary Adenoma

Pituitary adenomas are the anterior pituitary tumors. Patients with an Aryl Hydrocarbon Receptor-Interacting Protein (AIP) mutation (AIP- mut) tend to have more aggressive tumors occurring at a younger age. Single nucleotide polymorphisms (SNPs) in many studies have been related to metabolic comorbidities in the general population. Study aims investigated the role of AIP gene SNPs with susceptibility to acromegaly pituitary- adenoma, with levels of LH, FSH, TSH, Testosterone, IGF1,GH, FT4 , Prolactin hormones and blood sugar levels. The study ‎was conducted on a group of acromegaly patients, including 50 patients) both Genders( with ‎hyperplasia of the ends, and apparently healthy control group. Genotyping of AIP gene SNP (rs641081C >A‎) was indicated significant differences in frequency percentage between the study groups. The frequency of heterozygous CA genotype was significantly (p<0.01) higher in the patients' group when compared with control. The Means of IGF1, GH, prolactin, testosterone, and FBS were significantly ‎higher in patients at first treatment than that in control.‎ While,‎ the means of IGF1, GH, prolactin, and testosterone increased significantly in patients at last treatment than control. Patients mean level of TSH decreased significantly at last ‎treatment. No significant differences (P ≥ 0.05) were detected between study ‎groups in all other values.‎ The Means of IGF1, GH, and prolactin at first and last treatment were significantly decreased, while LH ‎was significantly increased at last treatment. In ‎patients with heterozygous mutant and wild genotype, means of IGF1, GH, and ‎prolactin decreased significantly at last treatment compared ‎to first treatment. ‎In this study heterozygous rs641081C>A showed a risk factor for susceptibility of acromegaly. Also, serum IGF1, GH, prolactin, were affected by the SNP of AIP gene within carriers of genotypes of rs641081C>A. IGF1, prolactin and GH ‎decreased significantly at last treatment compared to first treatment.

PD-L1 rs2890658 Polymorphism Increases Risk for Non-Small-Cell Lung Cancer in Northern China Population Based on Experimental Data and Meta-Analysis.

Purpose To dig the PD-L1 rs2890658 polymorphism with susceptibility of non-small-cell lung cancer (NSCLC) in northern China.Patients and MethodsThere were 600 NSCLC patients and 600 age and sex matched controls from the same ethnic origin recruited in the present research. Polymerase chain reaction-restriction fragment length polymorphism method genotyped PD-L1 rs2890658 polymorphism. PubMed and Embase were searched to get eligible literature for meta-analysis. The association between PD-L1 rs2890658 polymorphism and NSCLC risk was calculated with odds ratio and 95% confidence interval. Results It is more likely that individuals who have CC genotype and C allele are 2.15 and 1.41 times to develop NSCLC compared with individuals with AA genotype and A allele, respectively. Meta-analysis showed that the individuals who have C allele and CA genotype increased the risk of suffering from NSCLC. Conclusion PD-L1 rs2890658 polymorphism increased NSCLC risk in northern China population and it might predict the occurrence of NSCLC.

Correlations of FUT3 gene polymorphisms with colon polyps

ABSTRACT Objective: To explore the relationship between fut3 gene polymorphism and colonic polyps. Methods: Two hundred patients with colonic polyps and 200 healthy people in our hospital in recent 3 years were taken as the research objects, as the disease group and the control group, respectively. The disease group was divided into cancerous colonic polyps group (n = 50) and non-cancerous colonic polyps group (n = 150). The peripheral blood nucleated cells of the subjects were collected and isolated. The fut3 gene polymorphism was obtained by sequencing and analyzed combined with the expression of fut3 gene and the level of tumor markers. Results: The frequency of allele C at rs2561796 locus in the disease group was significantly higher than that in the control group (P < 0.05). The frequency of Ag genotype at rs441158 locus in the disease group was significantly higher than that in the control group, and the frequency of Ca genotype at rs2561796 locus was significantly lower than that in the control group (P < 0.05). In the disease group, the frequency of AA + Ag in the dominant model at rs441158 was significantly higher than that in the control group, and the frequency of Ca + AA in the invisible model at rs2561796 was significantly higher than that in the control group (P < 0.05). The frequency of CGC haplotype in the disease group was higher than that in the control group (P < 0.05). The linkage disequilibrium of rs441158 and rs2561796 loci of fut3 gene was high (d‘ = 0.423). The genotype of rs372725 of fut3 gene was correlated with the expression of fut3 gene (P < 0.05). The expression of fut3 gene in patients with CC genotype was significantly higher than that in patients with other genotypes (P < 0.05). Conclusion: fut3 gene polymorphism is associated with the susceptibility and carcinogenesis of colonic polyps.

Association of the Q141K polymorphism of the ABCG2 gene with the effectiveness of urate-lowering therapy in patients with gout (a pilot study)

Achieving the target serum uric acid (UA) level is a priority in the treatment of gout.Objective: to study the relationship of the ABCG2 gene polymorphism (rs2231142) with the efficacy of allopurinol and febuxostat in patients with gout.Patients and methods. The study included 82 patients with gout over 18 years of age with serum UA level &gt;360 μmol/L who did not take uratelowering therapy.All patients were prescribed allopurinol 100 mg daily, followed by its titration until the target UA level was reached (&lt;360 μmol/L or &lt;300 μmol/L in patients with chronic tofus gout), up to a maximum of 900 mg/day, in patients with glomerular filtration rate &lt;60 ml/min/1.73 m2 – up to 300 mg/day. Patients who did not reach the target UA level when using allopurinol were prescribed febuxostat 80 mg/day, which, if necessary, was increased to 120 mg/day. Monitoring of each patient was continued until the target serum UA level was reached.All patients underwent genotyping of the C&gt;A polymorphism (rs2231142) of the ABCG2 gene. We compared the probability of achieving the target UA level, the mean values of a decrease in the serum UA level, and the mean doses of urate-lowering drugs in patients with different genotypes (CC, CA, AA) of the ABCG2 gene.Results and discussion. The target UA level in 45 (55%) of 82 patients was defined as &lt;300 μmol/L, in the remaining 37 – as &lt;360 μmol/L.In 26 patients, the dose of allopurinol did not exceed 300 mg/day. In 28 (34%) patients treated with allopurinol, the target UA level was achieved, in the remaining 54 (66%) patients, allopurinol was substituted by febuxostat, and in 22 (41%) of them the UA level decreased and was below the target.The CC genotype of the ABCG2 gene was detected in 51 (62%) patients, the CA genotype in 30 (37%) and the minor genotype AA in 1 (1%).The probability of achieving the target UA level during therapy with allopurinol in carriers of homozygous CC genotype and genotypes CA or AA did not differ: 17 (33%) and 11 (35%) cases, respectively, but patients with CA and AA genotypes required a significantly higher dose of allopurinol (365±102 mg/day) than patients with the CC genotype (290±85 mg/day), p=0.002. Of the 54 patients who took febuxostat and did not reach the target UA level, 30 (56%) had the CC genotype and 24 (44%) had the CA genotype, the probability of reaching the target UA level was also comparable (p=0.22).Conclusion. The probability of reaching the target serum UA level in patients with gout taking allopurinol is not associated with the C&gt;A polymorphism of the ABCG2 gene, but the presence of CA and AA genotypes is identified with a higher dose of the drug. The C&gt;A (rs2231142) polymorphism of the ABCG2 gene does not affect the ability to achieve the goal of therapy when using febuxostat in patients with allopurinol ineffectiveness.

AURKC Gene Polymorphism (rs58264281) Associated with Idiopathic Male Infertility Risk in Northeast of Iran: A Case-Control Study

Background: Infertility is a major public health and social problem in human reproduction that is known as a multifactorial complex disorder. Genetic background and mutations and single nucleotide polymorphisms (SNPs) on the genes involved in sperm development are the important causes of male infertility. Objectives: In this study, we evaluated the association of AURKC gene polymorphism (rs58264281) and idiopathic male infertility in the Iranian Azeri population. Methods: This study was performed among 100 men with idiopathic infertility (case group) and 100 healthy men with successful fertility (control group) from East Azerbaijan, Iran. Genomic DNA extraction was carried out from peripheral blood samples by the proteinase K method. Genotype analysis was conducted by the tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS PCR). SPSS version 21 was used for the analysis of the obtained data. Results: We observed that the CA and AA genotypes were significantly increased in patients with infertility as compared to healthy controls. Our results demonstrated that the mutant allele of AURKC gene polymorphism (rs58264281) was a significant risk factor in male infertility. Conclusions: We suggested a significant correlation between the AURKC gene rs58264281 polymorphism and male infertility in the Iranian Azeri population. However, further studies are required among other ethnicities, races, and geographic areas with larger sample sizes.

SOCS3 Gene Polymorphism and Hypertension Susceptibility in Chinese Population: A Two-Center Case-Control Study.

Endothelial inflammation and vascular damage are essential risk factors contributing to hypertension. Suppressor of cytokine signaling 3 (SOCS3) is involved in the regulation of multiple inflammatory pathways. A large number of studies have shown that the anti-inflammatory effect of SOCS3 in hypertension, obesity, and allergic reactions has brought more insights into the inhibition of inflammation. Therefore, we selected a tagSNP of SOCS3 (rs8064821) to investigate whether they are contributing to the risk of hypertension in the Chinese population. In total, 532 patients with hypertension and 569 healthy controls were enrolled for two central of China. SOCS3 rs8064821 C>A polymorphism was genotyped using TaqMan assay. SOCS3 rs8064821 CA genotype was associated with an increased risk of hypertension (OR = 1.821, 95%CI = 1.276-2.600, P = 0.001). Rs8064821 A allele was associated with higher SOCS3 mRNA level in PBMCs from healthy donors. SOCS3 rs8064821 C>A polymorphism may contribute to the risk of hypertension in the Chinese population by regulating the expression of SOCS3.

Clinical Implications of MiR128, Angiotensin I Converting Enzyme and Vascular Endothelial Growth Factor Gene Abnormalities and Their Association with T2D.

Type 2 DM (T2D) results from the interaction of the genetic and environmental risk factors. Vascular endothelial growth factor (VEGF), angiotensin I-converting enzyme (ACE), and MicroRNAs (MiRNAs) are involved in important physiological processes. Gene variations in VEGF, ACE and MiRNA genes are associated with diseases. In this study we investigated the associations of the VEGF-2578 C/A (rs699947), VEGF-2549 insertion/deletion (I/D), and ACE I/D rs4646994 and Mir128a (rs11888095) gene variations with T2D using the amplification refractory mutation system PCR (ARMS-PCR) and mutation specific PCR (MSP). We screened 122 T2D cases and 126 healthy controls (HCs) for the rs699947, and 133 T2D cases and 133 HCs for the VEGF I/D polymorphism. For the ACE I/D we screened 152 cases and 150 HCs, and we screened 129 cases and 112 HCs for the Mir128a (rs11888095). The results showed that the CA genotype of the VEGF rs699947 and D allele of the VEGF I/D polymorphisms were associated with T2D with OR =2.01, p-value = 0.011, and OR = 2.42, p-value = 0.010, respectively. The result indicated the D allele of the ACE ID was protective against T2D with OR = 0.10, p-value = 0.0001, whereas the TC genotype and the T allele of the Mir128a (rs11888095) were associated with increased risk to T2D with OR = 3.16, p-value = 0.0001, and OR = 1.68, p-value = 0.01, respectively. We conclude that the VEGF (rs699947), VEGF I/D and Mir128a (rs11888095) are potential risk loci for T2D, and that the D allele of the ACE ID polymorphism may be protective against T2D. These results help in identification and stratification for the individuals that at risk for T2D. However, future well-designed studies in different populations and with larger sample sizes are required. Moreover, studies to examine the effects of these polymorphisms on VEGF and ACE proteins are recommended.

HIF-1α and VEGF polymorphisms and systemic lupus erythematosus susceptibility

BackgroundHypoxia-inducible factor-1α (HIF-1α) and its downstream gene, vascular endothelial factor (VEGF), play an important role in modulating the immune system function and consequently alternation the susceptibility to systemic lupus erythematosus (SLE) disease. ObjectiveThe present study aimed to investigate the effect of the HIF-1α and VEGF gene polymorphisms and the susceptibility to SLE. MethodsThe 140 patients and 150 healthy age and gender-matched people as a control group participated in the study. The PCR-RFLP method was used for genotyping. ResultsNo remarkable differences in allele frequencies of HIF-1α (rs11549465) and VEGF (rs699947) were seen between the SLE and control groups. The frequencies of CT genotype of the HIF-1α (rs11549465) and CA genotype of VEGF (rs699947) in the control were significantly higher than SLE group (OR = 0.53; 95% CI = 0.32–0.53; p = 0.014; OR = 0.57;95% CI = 0.33–0.99; p = 0.046, resp.). In the case of HIF-1α (C111A) polymorphism, the CA and AA variants were not found. ConclusionHIF-1α (rs11549465) CT and VEGF (rs699947) CA genotypes were identified as protective factors for SLE. However, additional studies are required to confirm the association between HIF-1α and VEGF polymorphisms and SLE.

Relationship between functional Nrf2 gene promoter polymorphism and sperm DNA damage in male infertility

ABSTRACT This study examines the association of the −617 C > A polymorphism in the Nrf2 gene (rs6721961) with male infertility in a Turkish population and determines its functional role in spermatogenesis in correlation with the impact of different levels of DNA damage on the genotypes. A total of 100 infertile men and 100 healthy fertile men were included in the study. Nrf2 genotyping was performed with the PCR-based restriction fragment length gene polymorphism (RFLP-PCR) analysis. According to our results, the Nrf2 CC, CA, and AA genotype distribution frequencies were 58.6%, 38.4%, and 3% in the control group, respectively, and 38%, 48%, and 14% in the infertile men, respectively. The AA genotype was significantly higher in the patient group. In smokers, a significant difference was found in progressive motility values between the genotypes (p = 0.001). Also, sperm progressive motility and concentration decreased significantly in those smokers with the AA genotype; smokers carrying this genotype were also 5.75 times more likely to have oligoasthenozoospermia than those with CC (p < 0.05). There was a significant relationship between the number of cases with high sperm-DNA damage when comparing the frequency of Nrf2 AA genotype carriers with the CC genotype 16.3% vs. 6.9%, respectively (p < 0.001). These results suggest the importance of the Nrf2 gene C > A (rs 6,721,961) polymorphism in the etiology of sperm DNA damage as a risk factor for male infertility. Smokers carrying the AA genotype are more likely to impair seminal parameters through antioxidant mechanisms. Abbreviations: Polymerase chain reaction (PCR)-based restriction fragment length gene polymorphism (RFLP-PCR); reactive oxygen species (ROS); deoxyribonucleic acid (DNA); catalases (CATs); superoxide dismutase (SOD); glutathione peroxidase (GPX); glutathione-S-transferase (GST); Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2); basic leucine zipper (bZIP); antioxidant response element (ARE); World Health Organization (WHO);normospermia(NS);asthenozoospermia(AS);oligozoospermia(OS);oligoasthenozoospermia (OAS); follicle stimulating hormone (FSH); ultraviolet (UV); low-melting-point agarose (LMA); normal-melting-point agarose (NMA); arbitrary units (AU); total comet score (TCS); A one-way analysis of variance (ANOVA); standard deviation (SD); N-acetyltransferase (NAT2); small non-coding RNAs (ncRNAs); microRNAs (miRNA)

MAD1L1 and TSNARE gene polymorphisms are associated with schizophrenia susceptibility in the Han Chinese population

BackgroundSchizophrenia (SCZ) is a severe mental illness with high heritability. This study aimed to explore the correlation between MAD1L1, TSNARE polymorphisms and SCZ susceptibility.MethodsA total of 493 SCZ patients and 493 healthy controls were included. The genotypes of MAD1L1 and TSNARE polymorphisms were identified by Agena MassARRAY platform. Odds ratio (OR) and 95% confidence intervals (CIs) were tested via logistic regression analysis in multiple genetic models and different subgroups.ResultsWe observed that AG genotype of rs1107592, AG genotype of rs4976976, and CA genotype of rs67756423 decreased the susceptibility to SCZ (p < 0.05). Age stratification analysis showed that the TC genotype of rs12666575, AG genotype of rs1107592, and AG genotype of rs4976976 decreased the risk of SCZ individuals older than 36 years (p < 0.05). In addition, the AG and AA genotype of rs4976976, the CA genotype of rs67756423 were associated with a lower risk of SCZ in males (p < 0.05). In females, the TT genotype of rs12666575 in recessive model, the AG and AA-AG genotype of rs1107592 in heterozygote and dominant model, could reduce the susceptibility to SCZ (p < 0.05). However, no significant association was found after Bonferroni correction.ConclusionsOur results suggest that MAD1L1 and TSNARE genetic polymorphisms exert a protective role in the risk of SCZ. These findings provide evidence that MAD1L1 and TSNARE may serve as potential biomarkers of SCZ. However, a replication experiment in a cohort with large sample size are required to confirm our findings.Trial registration Not applicable.

300Association between rs2231142 of ABCG2 and gout, hyperuricemia and uric acid: Systematic review and meta-analysis

Abstract Background Genome-wide association studies showed that rs2231142 (C421A) of ABCG2 gene has strong effects on gout and uric acid (UA). However, replication studies showed conflicting results. We aimed to pool effects of rs2231142 on gout, hyperuricemia, and UA across studies. Methods Studies were located from MEDLINE and Scopus until 17th June 2018. Data extractions were performed by two independent reviewers. Hardy-Weinberg equilibrium was checked. Genotype effects were pooled by ethnicity using mixed-effect logistic model for gout and hyperuricemia and multivariate meta-analysis for UA. Publication bias was assessed using funnel plots and Egger’s tests. Results Thirty studies were eligible; 21, 5, and 8 studies assessed association between rs2231142 and gout, hyperuricemia, and UA, respectively. Carrying AA and CA genotypes were 3.2 (2.4, 4.4) and 1.6 (1.5, 1.8) higher odds to develop gout in Caucasians. Likewise, in Asians, the ORs for corresponding genotypes were 4.5 (4.1, 5.0) and 2.1 (2.0, 2.3) for gout; 2.3 (1.8, 2.8) and 1.6 (1.4, 1.8) for hyperuricemia. Mean differences of UA in Caucasians carrying AA and CA were 50.4 (32.7, 68.2) and 19.5 (14.2, 24.7) µmol/l compared with those carrying CC genotype while in Asians, they were 18.4 (8.7, 28.1) and 11.5 (4.1, 18.9) µmol/l, respectively. Additive gene effects were suggested. Conclusions Significant effects of rs2231142 on gout, hyperuricemia, and elevated UA were confirmed. Our findings should be useful in personalized risk scores for prediction of gout and diseases related to high UA. Key messages rs2231142 increased the risk of gout and UA in Asians and Caucasians

Potential role of CMPK1, SLC29A1, and TLE4 polymorphisms in gemcitabine-based chemotherapy in HER2-negative metastatic breast cancer patients: pharmacogenetic study results from the prospective randomized phase II study of eribulin plus gemcitabine versus paclitaxel plus gemcitabine (KCSG-BR-13-11)

BackgroundIn this study, we evaluated the association between genetic polymorphisms of 23 genes associated with gemcitabine metabolism and the clinical efficacy of gemcitabine in breast cancer patients.Patients and methodsThis prospective, pharmacogenetic study was conducted in cooperation with a phase II clinical trial. A total of 103 genetic polymorphisms of the 23 genes involved in gemcitabine transport and metabolism were selected for genotyping. The associations of genetic polymorphisms with overall survival, progression-free survival (PFS), and 6-month PFS were analyzed.ResultsA total of 91 breast cancer patients were enrolled in this study. In terms of 6-month PFS, rs1044457 in CMPK1 was the most significant genetic polymorphism [55.9% for CT and TT and 78.9% for CC, P < 0.001, hazard ratio (HR): 4.444, 95% confidence interval (CI): 1.905-10.363]. For the rs693955 in SLC29A1, the median duration of PFS was 5.4 months for AA and 10.5 months for CA and CC (P = 0.002, HR: 3.704, 95% CI: 1.615-8.497). For the rs2807312 in TLE4, the median duration of PFS was 5.7 months for TT and 10.4 months for CT and CC (P = 0.005, HR: 4.948, 95% CI: 1.612-15.190). In survival analysis with a multi-gene model, the TT genotype of rs2807312 had the worst PFS regardless of other genetic polymorphisms, whereas the CA genotype of rs693955 or the CT genotype of rs2807312 without the AA genotype of rs693955 had the best PFS compared with those of other genetic groups (P < 0.001).ConclusionsGenetic polymorphisms of rs1044457 in CMPK1, rs693955 in SLC29A1, and rs2807312 in TLE4 were significantly associated with the 6-month PFS rate and/or the duration of PFS. Further studies with a larger sample size and expression study would be helpful to validate the association of genetic polymorphisms and clinical efficacy of gemcitabine.

Analysis of bone metabolism mechanisms in postmenopausal females with type 2 diabetes and DKK1 gene polymorphisms and the effects of polymer nanomaterials on wound infection in patients

Diabetic patients are prone to abnormal bone metabolism. Menopausal women exhibit reduced estrogen secretion and bone absorption exceeds the rate of bone formation. Therefore, postmenopausal women with diabetes are even more likely to suffer from osteoporosis. Identifying the specific mechanism of abnormal bone metabolism in diabetic menopausal women will help reduce the risk of bone fractures. This study explored the specific mechanisms of bone metabolism disorders in menopausal women with type 2 diabetes in relation to genetic polymorphisms. We found that the distribution frequency of the CA genotype and A allele at the rs1373004 locus of the DKK1 gene in menopausal women with diabetes and abnormal bone mass were significantly lower compared with that in normal bone. The distribution of the GG genotype at the rs1528877 locus was also less frequent compared with those exhibiting normal bone mass. This suggests that the genotype and allele frequency distribution in the DKK1 gene at rs1373004 and RS1528877 in postmenopausal T2DM women is associated with glucose metabolism and bone metabolism. To analyze the efficacy of polylactic acid (PLA)/gelatin nanofibers on T2DM patients with infectious fractures, we compared various aspects of wound healing in patients treated with conventional therapy versus PLA/gelatin nanofibers. The results indicated that the number of days required for wound healing and the frequency of incisions in patients treated with PLA/gelatin nanofibers were significantly lower compared with those treated with conventional therapy (P &lt; 0.05). The wound healing rate of patients treated with PLA/gelatin nanofibers was significantly higher compared with that of patients treated with conventional therapy on days 7, 14, 21, and 28 of treatment. Our findings indicate that PLA/gelatin nanofiber treatment can significantly promote fracture wound healing.

CCR4 1014C/T and CCL22 16C/A Genetic Variations in the Iranian Patients with Thyroid Cancer

Background: The aim of this study was to investigate the association between thyroid cancer and 16C/A single nucleotide polymorphism (SNP) in C-C motif chemokine 22 (CCL22) as well as 1014C/T SNP in C-C chemokine receptor type 4 (CCR4). Method: In this case-control study, Polymerase Chain Reaction Restriction-Fragment Length Polymorphism (PCR-RFLP) was performed for 113 thyroid cancer patients and 112 age-sex matched healthy controls to investigate the genotype distribution. Results: At position 16C/A in CCL22, 95 patients (84.3%) were found to have CC genotype while 17 individuals (14.8%) inherited CA genotype and 1 (0.9%) had AA genotype. In the control group, 92 volunteers (82.1%) inherited CC genotype, 18 individuals (16.1%) had CA genotype, and 2 (1.8%) had AA genotype. The frequency of CC, CT, and TT genotypes of 1014C/T SNP in CCR4 gene was 60 (53.1%), 43 (38.1%), and 10 (8.8%) in the patients, and 57 (53.3%), 43 (40.2%), and 7 (6.5%) in the control group, respectively. There were no statistically significant differences between the patients and controls in terms of 16C/A polymorphism in CCL22 (P= 0.816) and 1014C/T SNP in CCR4 1014C/T gene position (P=0.801). Nevertheless, the study of their association indicated that inheriting the CC genotype of CCR4 is significantly associated with higher stages (stages 3 and 4) in thyroid cancer. Conclusion: 1014C/T genetic variation in CCR4 and 16C/A polymorphism in CCL22 were not found to have a role in the incidence of thyroid cancer. Inheriting CC genotype at 1014 locus in CCR4 may, however, affect cancer progression in patients with thyroid cancer.

Identification of&amp;lt;italic&amp;gt; StDRO1&amp;lt;/italic&amp;gt; gene polymorphism and association analysis with root traits in potato

<p id="C3">In order to identify the single nucleotide polymorphism (SNP) of <italic>StDRO1</italic> gene associated with potato root traits, <italic>StDRO1</italic> gene coding region of the 110 tetraploid potato genotypes was cloned and sequenced. The association analysis between the <italic>StDRO1 </italic>SNPs and the major root traits of potato such as surface area, volume, and average diameter were carried out. The results showed that a SNP (G64C) was detected in the second exon of the <italic>StDRO1</italic>, 10 SNPs (G152A, A214G, A297G, C314T, A337T, T353C, T560A, C577A, C620A, and C625A) were identified in the third exon, and a SNP (T793A) was detected in the fourth exon. The association analysis indicated that in the total root volume, G152A locus of <italic>StDRO1</italic> gene showed that GA genotype was superior to GG genotype (<italic>P</italic> &lt; 0.05). In the average root diameter, C314 locus showed that CC genotype were superior to CT genotype (<italic>P </italic>&lt; 0.05). In the root surface area, fresh weight, and dry weight, A337T locus showed that AT genotype were better than AA genotype (<italic>P </italic>&lt; 0.05), while the locus in the average root diameter showed that AT genotype was significantly lower than AA genotype (<italic>P </italic>&lt; 0.05). The root surface area, root volume, and fresh weight were showed as TC genotype &gt; TT genotype (<italic>P </italic>&lt; 0.05) in T353C site; the root volume was showed as CA genotype &gt; CC genotype (<italic>P </italic>&lt; 0.05) in C620A site; the root surface area, root volume, and fresh weight were showed as AT genotype &gt; TT genotype (<italic>P </italic>&lt; 0.05) in T793A site. In summary, the above six SNPs of <italic>StDRO1</italic> genes had a significant impact on potato root traits, and the A337T, T353C, and T793A sites were particularly important. These results provide a basic theoretical reference for subsequent potato root architecture research and genetic improvement, but whether it could be used as a genetic marker for potato root traits need to be further verified by expanding the population sample.

Vitamin D receptor gene polymorphisms and its interactions with environmental factors on renal cell carcinoma risk

AimsWe designed a case-control study to investigate the effect of vitamin D receptor gene (VDR) gene single nucleotide polymorphisms (SNPs) and possible gene- environment interaction on the susceptibility of renal cell carcinoma (RCC).MethodsGeneralized multifactor dimensionality reduction (GMDR) was used to find out the interaction combinations between SNPs and environmental factors, including gene- gene synergy and gene environment synergy effect. Logistic regression was used to analyze the correlation between the four SNPs in VDR gene and RCC, and the significant interaction combinations found by GMDR model were analyzed by hierarchical analysis.ResultsThe genotype distribution of the control group was in accordance with Hardy- Weinberg equilibrium. Logistic regression analysis showed that the risk of RCC in VDR-rs7975232 A allele carriers was significantly higher than that of CC genotype carriers (CA + AA vs. CC), adjusted OR (95 % CI) = 1.75 (1.26–2.28). We used GMDR model to screen the best synergistic model between the four SNPs of VDR gene and smoking and drinking. We found a significant two locus model (P = 0.0010) involving rs7975232 and smoking. The cross- validation consistency of the two- locus model was 10/ 10, and the accuracy was 60.72 %. Compared with non-smokers with rs7975232 -CA or AA genotype, smokers with rs7975232 -CC genotype had the highest risk of RCC, or (95 % CI) = 2.23 (1.42–3.09), after adjustment for covariates.ConclusionsWe found that the A allele of rs7975232 within VDR gene, interaction between rs7975232 and smoking were all associated with increased RCC risk.

Association of FOXP3 rs3761548 polymorphism and its reduced expression with unexplained recurrent spontaneous abortions: A South Indian study.

Fork Head Box Protein 3 (FOXP3) is an X-linked gene, codes for a master transcription regulatory protein that controls the development and function of immunosuppressive T regulatory (Treg) cells. They are crucial mediators of maternal foetal tolerance and successful pregnancy outcome. The aim of the study is to evaluate the association of FOXP3 rs3761548 functional polymorphism and to assess the serum concentrations of full-length FOXP3 protein in Unexplained Recurrent Spontaneous Abortions (URSA) patients of Southern India. The study included blood samples from 150 URSA patients and 150 healthy, pregnant parous women. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism was done for rs3761548 FOXP3 genotyping. Serum concentrations of full-length FOXP3 protein were estimated by enzyme-linked immunosorbent assay. The frequencies of mutant A allele, CA and AA genotypes of rs3761548 functional polymorphism were significantly elevated in patients compared to healthy, pregnant parous women and exhibited a two, three and twofold increased risk respectively towards URSA. Serum concentrations of full-length FOXP3 protein were high in controls compared to patients (10.14±.30 vs. 8.84±1.73ng/ml; p<.05). Our results advocate an association of FOXP3 rs3761548 polymorphism and reduced expression of full-length FOXP3 protein with URSA.

POLG Gene Variants in Cervical Cancer Patients and Their Associations with Clinical and Pathomorphological Tumor Characteristics.

Cervical cancer is one of the most common cancers in women worldwide. Human papillomaviruses are known to be the main, but not the only risk factor, of this cancer type. Despite all the knowledge on this cancer type, it is still a challenge to predict the course of the disease, and therefore, minimally invasive biomarkers are needed. This study aimed to analyze single-nucleotide variants in the POLG gene and assess the associations with tumor phenotype and patient outcome. A total of 172 cervical cancer patients were included in this study. Clinical and tumor data were gathered from medical records retrospectively. Single nucleotide variations were determined using TaqMan probes with Real-Time PCR. Significant associations between POLG rs3087374 and cervical cancer patients’ tumor histological type, stage, and tumor size were determined. The CA genotype and A allele of rs3087374 increased the probability of adenocarcinoma histological tumor type, IIIA stage, and T3 tumor size compared to CC genotype and C allele, respectively. Furthermore, patients with AA genotype in rs2072267 had longer metastasis-free survival than those with the GG genotype. Our data suggest that mitochondrial polymerase gamma encoded by nuclear POLG gene is important for specific tumor phenotype formation and patient outcome in cervical cancer.

Polymorphism of TUSC7 associated with gastric cancer susceptibility and binding with miR-133a-3p: a population-based case-control study.

Previous studies have demonstrated that gene polymorphism is associated with cancer susceptibility. Most of these genes are involved in neoplastic processes. Previous studies demonstrated that tumor-suppressor candidate 7 (TUSC7) was a tumor-suppressor gene in various tumors. This study aims to explore the association between lncRNA TUSC7 polymorphism and gastric cancer susceptibility and the potential function. The tagging SNPs of TUSC7 were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a Chinese Han population-based case-control study. The relative expression level of TUSC7 in plasma was conducted by quantitative real-time PCR (qRT-PCR). The gene-environment interaction was analyzed by multifactor dimensionality reduction (MDR). The dual luciferase reporter assay was used to examine whether SNP rs12494960 of TUSC7 allele variation affected the binding of lncRNA-TUSC7 and miRNAs miR-133a-3p. Three tagging SNPs (rs12494960, rs1518338, rs2867837) of TUSC7 were selected to validate in population. The unconditional multiple logistic regression showed that individuals with genotype AA (OR: 1.79, 95% CI: 1.16, 2.70) of rs12494960 and GG (OR: 2.24, 95% CI: 1.12, 4.46) of rs2867837 in TUSC7 had increased risk of GC susceptibility. The qRT-PCR showed that CA and AA genotype of rs12494960 in TUSC7 had significantly lower relative expression level in plasma, compared with CC genotype. The dual luciferase reporter assay showed that TUSC7 and miR-133a-3p had interaction. The mutant genotype of rs12494960 could increase the susceptibility of gastric cancer and might affect the corresponding mRNA expression of lncRNA TUSC7 in plasma.