TNFA -308G>A and IL10 -1082A>G Polymorphisms as Predictive Biomarkers of Chronic HCV Infection

Genetic changes may induce dysregulated cytokine production and affect the progression of the chronic disease caused by the hepacivirus C (HCV) because the balance of pro- and anti-inflammatory cytokines determines the outcome of infection. This study evaluated the TNFA − 308G > A and IL10 -1082A > G polymorphisms in the susceptibility and progress of chronic hepatitis C. The study included 101 samples from patients with chronic hepatitis C and 300 samples from healthy donors. Polymorphisms were typed by real-time PCR and were analyzed for associations with histopathological parameters (according to METAVIR classification) and HCV viral load. The polymorphic genotype for the TNFA − 308G > A variant was not present in the group of patients with chronic hepatitis C and was associated with protection against HCV infection (p = 0.0477). Patients with the polymorphic genotype of the IL10 -1082A > G polymorphism had higher HCV viral load than wild-type patients (p = 0.0428). Neither polymorphism was associated with different levels of necroinflammatory activity or fibrosis scores. The polymorphic genotype at TNFA − 308G > A protected against chronic HCV infection, and the polymorphic genotype at the IL10 -1082A > G variant was associated with viral persistence.

The TNFA -308G>A and IL10 -1082A>G Polymorphisms as Predictive Biomarkers of Chronic HCV Infection

Background: Genetic changes may induce dysregulated cytokine production and affect the progression of the chronic disease caused by the hepacivirus C (HCV) because the balance of pro- and anti-inflammatory cytokines determines the outcome of infection. This study evaluated the TNFA -308G>A and IL10 -1082A>G polymorphisms in the susceptibility and progress of chronic hepatitis CMethods: The study included 101 samples from patients with chronic hepatitis C and 300 samples from healthy donors. Polymorphisms were typed by real-time PCR and were analyzed for associations with histopathological parameters (according to METAVIR classification) and HCV viral load. Results: The polymorphic genotype for the TNFA -308G>A variant was not present in the group of patients with chronic hepatitis C and was associated with protection against HCV infection (p = 0.0477). Patients with the polymorphic genotype of the IL10 -1082A>G polymorphism had higher HCV viral load than wild-type patients (p = 0.0428). Neither polymorphism was associated with different levels of necroinflammatory activity or fibrosis scores. Conclusion: The polymorphic genotype at TNFA -308G>A protected against chronic HCV infection, and the polymorphic genotype at the IL10 -1082A>G variant was associated with viral persistence.

An Analysis of Five TrkB Gene Polymorphisms in Schizophrenia and the Interaction of Its Haplotype with rs6265 BDNF Gene Polymorphism

Aim. The BDNF dysfunction in the schizophrenia has been soundly documented. The TrkB gene is a high-affinity receptor of the BDNF that is changed in schizophrenia and mood disorders. The study had two aims: first, to identify whether the five nucleotide polymorphisms (SNPs) in TrkB gene are associated with a diagnosis of schizophrenia; and the latter, if any association exists between the TrkB SNPs and psychopathology, suicide attempts, and family history of schizophrenia in a Caucasian population. Methods. Case-control study (401 patients and 657 healthy controls) was used to examine a predisposition for schizophrenia. The tests for psychopathology, suicide attempts, and family history of schizophrenia were conducted only in patient group. The severity of the schizophrenia was measured using the five-factor model of the PANSS. In addition, the haplotype analysis for both the separate for SNPs of TrkB gene and in combination with the rs6265 SNP BDNF gene was conducted. Results. Our case-control study revealed that the genetic variants of rs10868235 (T/T polymorphic genotype) and rs1387923 (G/G polymorphic genotype) of the TrkB gene were associated with a higher risk of developing schizophrenia in men. However, the A/A wild genotype of rs1387923 was connected with a lower risk for both the development of and the family manifestation of schizophrenia in men. The G polymorphic allele of rs1565445 was associated with an increased risk of suicide in schizophrenia. The tested SNPs of the TrkB gene did not modulate the psychopathology of schizophrenia. The haplotype that was built with five SNPs in the TrkB gene was protective for men, but after joining the rs6265 SNP of the BDNF gene, a haplotype that was protective for women was created.

Haplotypes in BMP4 and FGF Genes Increase the Risk of Peri-Implantitis

Despite the success of osseointegrated implants, failures have increased significantly, associated with development of peri-implantitis. Multiple factors influence the peri-implant bone loss, including environmental and genetic causes. BMPs (Bone morphogenetic proteins) are growth factors that induce bone formation. FGF (fibroblast growth factors) and their receptors (FGFRs) play important roles by controlling the levels of cell proliferation, differentiation and migration. BMP/FGF relationship is responsible for promoting bone regeneration and bone loss. The aim of this study was to analyze the correlation between BMP4, FGF3, FGF10 and FGFR1 genes and peri-implant bone loss. Two hundred and fifteen volunteers, with 754 dental implants, were submitted to oral examination and divided in healthy group (n=129) and peri-implantitis group (n=86). Thirteen polymorphisms in BMP4, FGF3, FGF10 and FGFR1 genes were analyzed individually and in haplotype. The chi-square test correlated genotypes, allelic and haplotype frequencies. Values of p<0.05 were considered significant. Volunteers with peri-implantitis demonstrated high incidence of total edentulism (p<0.0001) and thin peri-implant phenotype (p<0.04). Higher incidence of spontaneous bleeding, plaque and implant mobility was observed in peri-implantitis group (p<0.0001 for all). The TT polymorphic genotype for BMP4 rs2761884 was associated with healthy peri-implant (p=0.01). FGF3 rs4631909 (TT+CT genotype) also showed association with the control group (p=0.04). The frequency of C allele for FGF3 rs4631909 showed a tendency for association with peri-implantitis (p=0.08). FGF10 CCTG (p=0.03), BMP4 GAAA (p=0.05) and GGGA (p=0.02) haplotypes were associated with peri-implantitis (p=0.03). Therefore, it may be concluded that BMP4 and FGF10 haplotypes are associated with peri-implantitis.

Association of TNF-α rs-281865419 polymorphism with reproductive tract infections in Indian population

Aim: To investigate the presence of reproductive tract infections (RTIs) in symptomatic and asymptomatic women in North India and association of SNPs in TNFα gene (rs-281865419 C/T) with susceptibility to these RTIs. Methods: We collected 100 symptomatic (cases) and 100 asymptomatic women (controls) samples and screened them for RTIs. Then genotyping of TNF-α gene was performed by PCR-RFLP. Results: Among cases the frequencies of RTIs infection is higher than control. The prevalence of HPV, C. trachomatis, T. vaginalis, Bacterial vaginosis and N. gonorrhoeae are 28% & 6%; 11%, 32% respectively while in controls it was 5%, 2%, 1% and 8% & 1%. In the present study we found that the frequency of wild homozygous genotype (TT) was lower in cases 30% (6/20) as compared to controls 60% (12/20). The frequency of the heterozygous polymorphic genotype (CT) was higher in cases 65% (65/100) as compared to controls 32% (32/100). It was interesting to note that the frequency of the polymorphic homozygous genotype (CC) was higher in cases 15% (15/100) than controls 2% (2/100). While the frequency of the carrier genotype (CT + TT) was found to be more in cases 70% (70/100) than in controls 40/100 (40%). This study shows that T allele may be risk factor for Reproductive tract infections as its percentage is higher in cases as compare to normal controls. Conclusion: TNF-? rs-281865419 locus may serve as an important biomarker for RTIs predisposition in Indian population though larger sample size is needed to validate the findings.

Association of TNF-α–rs 281865419 polymorphism with reproductive tract infections in Indian population

Aim: To investigate the presence of reproductive tract infections (RTIs) in symptomatic and asymptomatic women in North India and association of SNPs in TNF? gene (rs-281865419 C/T) with susceptibility to these RTIs. Methods: We collected 100 symptomatic (cases) and 100 asymptomatic women (controls) samples and screened them for RTIs. Then genotyping of TNF-? gene was performed by PCR-RFLP. Results: Among cases the frequencies of RTIs infection is higher than control. The prevalence of HPV, C. trachomatis, T. vaginalis, Bacterial vaginosis and N. gonorrhoeae are 28% and 6%; 11%, 32% respectively while in controls it was 5%, 2%, 1% and 8% and 1%. In the present study we found that the frequency of wild homozygous genotype (TT) was lower in cases 30% (6/20) as compared to controls 60% (12/20). The frequency of the heterozygous polymorphic genotype (CT) was higher in cases 65% (65/100) as compared to controls 32% (32/100). It was interesting to note that the frequency of the polymorphic homozygous genotype (CC) was higher in cases 15% (15/100) than controls 2% (2/100). While the frequency of the carrier genotype (CT + TT) was found to be more in cases 70% (70/100) than in controls 40/100 (40%). This study shows that T allele may be risk factor for reproductive tract infections as its percentage is higher in cases as compare to normal controls. Conclusion: TNF-? rs-281865419 locus may serve as an important biomarker for RTIs predisposition in Indian population though larger sample size is needed to validate the findings.

Genetic Variants in Folate and Cobalamin Metabolism-Related Genes in Nonsyndromic Cleft Lip and/or Palate

The aim of this study was to evaluate the association of the polymorphisms in TCN2 (rs1801198) gene and in MTRR (rs1801394) gene with nonsyndromic cleft lip and/or palate (NSCL/P) in a Brazilian population. Genomic DNA was extracted from buccal cells. The polymorphisms in TCN2 (rs1801198) and MTRR (rs1801394) genes were genotyped by carrying out real-time PCR and Taqman assay. Chi-square test was used to determine the association between genotype and allele frequencies with NSCL/P and NSCL/P subgroups (cleft lip only, cleft lip and palate, and cleft palate only). Eight hundred and sixty seven unrelated individuals (401 cases with NSCL/P and 466 individuals without cleft) were evaluated. Genotype distributions of TCN2 and MTRR polymorphisms were in Hardy-Weinberg equilibrium. The TCN2 polymorphic genotype GG was identified in 16.7% of the NSCL/P group and in 14.1% of the non-cleft group (p>0.05). Similarly, the frequency of MTRR genotype (GG) was similar in NSCL/P group (15.5%) and control group (17.8%) (p>0.05). Multivariate analysis showed an association between MTRR and the subgroup that the mother smoked during pregnancy (p=0.039). Our findings did not demonstrate an association between TCN2 polymorphisms and NSCL/P, however suggests an association between MTRR and NSCL/P etiology

Association of Sweet Taste Receptor Gene Polymorphisms with Dental Caries Experience in School Children

Sweet taste is a powerful factor influencing food acceptance. The peripheral taste response to sugar is mediated by the TAS1R2/TAS1R3 taste receptors. The aim of the study was to determine the relationship between TAS1R2 (rs35874116 or rs9701796) and/or TAS1R3 (rs307355) single nucleotide polymorphisms with dental caries experience in schoolchildren. A total of 184 schoolchildren aged between 7 and 12 years (101 girls, 83 boys) were included in the study. Genomic DNA was extracted from saliva samples and the genotypes were identified by qPCR. The genotype frequencies were as follows: 6.6% for homozygous wild type, 41.8% for heterozygous and 51.6% for homozygous polymorphic genotype carriers of TAS1R2 gene rs35874116; 27.8% for heterozygous and 72.2% for homozygous polymorphic genotype carriers of TAS1R2 gene rs9701796, and 83.1% for homozygous wild type and 16.9% for heterozygous genotype carriers of TAS1R3 gene rs307355 polymorphism. A significant association was observed between total caries experience (dft + DMFT - decayed filled primary teeth + decayed, missing and filled permanent teeth) and TAS1R2 rs35874116 (p = 0.008) and TAS1R3 rs307355 (p = 0.04) gene polymorphisms but not for TAS1R2 gene rs9701796 polymorphism. TAS1R3 gene rs307355 polymorphism has been found to be an independent risk factor for dental caries experience by logistic regression analysis and to have increased the risk of caries. Moderate caries experience (4-7 caries) was found to be associated with TAS1R3 rs307355 heterozygous genotype, whereas high-risk caries experience (>8 caries) was found to be associated with TAS1R2 rs35874116 homozygous polymorphic genotype.

Genetic variation in exon 17 of INSR is associated with insulin resistance and hyperandrogenemia among lean Indian women with polycystic ovary syndrome

ObjectivePolycystic ovary syndrome (PCOS) is a multigenic disorder, and insulin resistance is one of its hallmark features. Polymorphisms in exon 17 of insulin receptor (INSR) gene are reported to be associated with PCOS. We investigated this association in Indian women and its putative relationship with PCOS associated traits, which has not been explored so far.MethodsIn this case control study, the polymorphisms were investigated by direct sequencing in 180 women with PCOS and 144 age matched controls. Clinical, anthropometric, biochemical, and hormonal parameters were also estimated.ResultsThe silent C/T polymorphism at His1058 in exon 17 of INSR was found to be present in our study population. The polymorphic genotype (CT+TT) was significantly associated with PCOS in lean women (χ2=8.493, df=1, P=0.004). It showed association with higher fasting insulin levels (P=0.02), homeostasis model assessment of insulin resistance (P=0.005), free androgen index (P=0.03), and lower quantitative insulin sensitivity check index (P=0.004) in lean PCOS women. No other novel or known polymorphism was identified in exon 17 in this cohort.ConclusionsThe study shows significant association of C/T polymorphism at His1058 of INSR with PCOS in the lean rather than obese Indian women. Its association with indices of insulin resistance and hyperandrogenemia is also seen in the same group. The findings strengthen the concept that pathogenesis of PCOS is different in lean and obese women.