Endometrial receptivity defects MUC-1 and COX-2 polymorphisms in endometriosis.

The endometrium produces MUCIN-1 (MUC-1) and cyclooxygenase-2 (COX-2), which are essential for implantation. MUC-1 is required for adhesion, while COX-2 is necessary for decidualization. Variations or polymorphisms in MUC-1 and COX-2 can lead to changes in endometrial receptivity. This study investigated the relationship between MUC-1 and COX-2 polymorphisms and endometrial receptivity in endometriosis patients. Blood DNA samples were collected from 35 patients with endometriosis and 32 healthy patients between days 19 to 24 of their menstrual cycle (secretory phase). MUC-1 polymorphism was determined using the Amplification Refractory Mutation System (ARMS), and COX-2 gene polymorphism was assessed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The frequency distribution of gene polymorphisms between the two groups was compared using bivariate analysis. There were seven genotypic combinations of MUC-1 and COX-2: AAGC; AAGG; GACC; GAGC; GAGG; GGGC; GGGG. The AAGC genotype combination test was significant, with an OR=6.43 (95% CI:1.09-7.62) and p=0.01. In conclusion, combining MUC-1 and COX-2 (AAGC) genotypes results in endometrial receptivity defects in endometriosis.

Assessment of the Link of ABCB1 and NR3C1 gene polymorphisms with the prednisolone resistance in pediatric nephrotic syndrome patients of Bangladesh: A genotype and haplotype approach.

Introduction: Nephrotic syndrome is a common pediatric kidney disease. Investigations on several genetic polymorphisms revealed an inconsistent influence on the resistance of patients to steroids. Objectives: This study aimed to identify the association of ABCB1 (1236C > T, 2677G > T, 3435C > T), NR3C1 (rs10482634, rs6877893), and CYP3A5 (CYP3A5*3) gene polymorphism as well as sociodemographic and clinicopathological parameters with the risk of developing prednisolone resistance in pediatric patients with nephrotic syndrome. Methods: A case-control analysis was performed on 180 nephrotic syndrome patients. Among them, 30 patients were classified as prednisolone resistant group, and 150 were classified as prednisolone sensitive group. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: No significant association of 1236C > T polymorphism with the risk of prednisolone resistance (p > 0.05) was found. The GT heterozygous of 2677G > T was found to be significantly associated with the development of prednisolone resistance (OR = 3.9, p = 0.034). In the case of 3435C > T, a statistically significant association was observed in TC heterozygous and TT mutant homozygous genotypes (OR = 0.38, p = 0.047; OR = 3.06, p = 0.038, respectively) with prednisolone resistance. For rs10482634 polymorphism, the AG heterozygous and AG+GG genotypes were significantly linked with prednisolone resistance (OR = 2.40, p = 0.033; OR = 2.36, p = 0.034, respectively). We found no association with the risk of prednisolone resistance with rs6877893 and CYP3A5*3 polymorphism (p > 0.05). CTC and TGT haplotypes of ABCB1 and GA haplotype of NR3C1 were also associated with the increased risk of pediatric prednisolone resistance (OR = 4.47, p = 0.0003; OR = 2.71, p = 0.03; and OR = 4.22, p = 0.022, consecutively). We also observed the correlation of different sociodemographic and clinicopathological factors with prednisolone resistance in pediatric nephrotic syndrome. Conclusion: Our findings showed a significant association of ABCB1 and NR3C1 gene polymorphisms with prednisolone resistant pediatric nephrotic syndrome.

Association of 5'UTR polymorphism of secretory phospholipase A2 group IIA (PLA2G2A) gene with prostate cancer metastasis.

Phospholipase A2 (PLA2) enzymes are small lipolytic hydrolases that can regulate immune responses through generation of Arachidonic Acid (AA), a precursor molecule of lipid mediators like prostaglandins, leukotrienes and thromboxanes. One of the family members of PLA2, secretory Phospholipase A2 Group IIA (PLA2G2A), was associated with different types of malignancies including prostate cancer. Elevated serum levels of PLA2G2A was found in prostate cancer (PCa) patients and associated with increased tumor grade in literature. 5'UTR regions have regulatory role in protein expression by controlling the accessibility of factors necessary for the translation initiation. Single nucleotide polymorphisms at 5'UTR regions have the potential to affect mRNA translation efficiency resulting in altered protein levels depending on structure and nucleotide content. Given that the 5'UTR polymorphism in PLA2G2A gene (rs11573156) is associated with increased serum levels of PLA2G2A, the association of this 5'UTR polymorphism with PCa susceptibility and metastasis was investigated in this study. Total of 261 PCa patients and 128 control individuals were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Individuals with heterozygous CG genotype was found to have significantly reduced risk of PCa metastasis with an Odds Ratio (OR) of 0.405 (p = 0.028, 95%CI = 0.181-0.906), compared to the carriers of homozygous CC genotype (p > 0.05) suggesting an anti-metastatic effect for the G allele. No association was found between PCa susceptibility and Gleason score (p > 0.05) in Turkish population.

Detection of KIT mutations in core binding factor acute myeloid leukemia.

We have investigated the frequency and the effect of KIT mutations on the outcome of patients with CBF-AML. 69 patients (34 pediatrics and 35 adults) with CBF-AML were enrolled in the study. The frequency of KIT mutations was higher in adults compared to pediatrics (22.9% and 14.7%, p = 0.38) respectively. Leukocytosis ≥ 20 × 109 /L was significantly associated with pediatrics compared to adults. t(8;21)(q22;22) was significantly associated with thrombocytopenia in adults. We conclude that no significant difference is found between KIT mutated and unmutated CBF-AML in adults and pediatrics. Children with CBF-AML present with leukocytosis. t(8;21) is associated with thrombocytopenia.

Association between GNB3 c.825C > T polymorphism and the risk of overweight and obesity: A meta-analysis.

BACKGROUND: The association between G protein ß-polypeptide 3 gene (GNB3) c.825C > T polymorphism (rs5443) and the risk of overweight/obesity has been investigated in many published studies, but the results were conflicting and inconclusive. A meta-analysis was performed to make a more accurate assessment of the relationship. METHODS: The PubMed, ProQuest Health & Medical Complete, Web of Science, Chinese Biomedical Medical databases (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wan Fang databases were searched to identify eligible literatures. Pooled odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were used to assess the strength of association between GNB3 c.825C > T polymorphism and overweight/obesity. RESULTS: Eleven articles including 15 case-control studies with a total of 10,396 subjects (3171 cases of overweight/obesity and 7225 controls) were enrolled in the meta-analysis. The GNB3 c.825C > T was significantly associated with overweight/obesity under a recessive model (OR = 1.22, 95% CI: 1.04-1.44, P = 0.015). Moreover, the GNB3 825T allele was obviously associated with overweight alone in all inheritable models (P < 0.05) except in a recessive model (P = 0.084). In the stratification analysis by potential confounding variables, a significant association was observed between GNB3 c.825C > T polymorphism and overweight/obesity risk in males under an allelic model (P = 0.008), a homozygous model (P = 0.014), a recessive model (P = 0.005), and a dominant model (P = 0.049). And the results also showed that GNB3 c.825C > T polymorphism was significantly associated with overweight/obesity in subgroups of mean age less than 30 years, consistent with HWE, and high-quality studies (P = 0.027, P = 0.043, P = 0.040, respectively) under a recessive model, but not in other subgroups. Meta-regression also revealed that P value of HWE, publication year, and the quality scores of studies were the sources of heterogeneity in a recessive model and an allelic model. "Leave one out" sensitivity analyses indicated that the association was more significant after excluding some studies. The funnel plot and Egger's linear regression test and Begg's test revealed no apparent publication bias. CONCLUSION: This meta-analysis suggests that the presence of TT homozygote might be one of the genetic factors susceptible to overweight/obesity and that males or aged under 30 years increase the genetic susceptibility.

Investigation of the monocyte diapedesis-related LFA-1 and JAM-A gene variants in Turkish coronary heart disease patients.

BACKGROUND: LFA-1/JAM-A interaction plays a significant role in early steps of leukocyte transendothelial migration (diapedesis) which takes part in atherosclerosis pathogenesis. In this population-based case-control study, the frequencies of JAM-A rs790056 and LFA-1 rs8058823 gene polymorphisms in patients with coronary heart disease (CHD) and healthy subjects were investigated and the correlations between the different genotypes and cardiovascular risk factors were analyzed. METHODS: The JAM-A and LFA-1 genotypes were determined in 153 patients with CHD and 124 controls by PCR-RFLP assay. RESULTS: In CHD patient group, the frequency of JAM-A rs790056 TT genotype and the frequency of T allele were higher when compared with the control group (p = 0.03 and p = 0.007,respectively). In patient groups, the frequency of LFA-1 rs8058823 AA genotype was higher (p = 0.000), and the frequency of AG genotype was lower when compared with the control group (p = 0.031). In the control group, LFA-1 rs8058823 G allele carriers had higher SBP than subjects with AA genotype (p = 0.038), whereas in the CHD patient group, G allele carriers had lower DBP than subjects with AA genotype (p = 0.007). The multivariate logistic regression analysis confirmed that the JAM-A rs790056 TT genotype (OR = 2.472, p = 0.045) and LFA-1 rs8058823 AA genotype (OR = 6.751, p = 0.000) were risk factors for CHD development. CONCLUSION: These results suggest that the wild type genotypes and alleles of JAM-A rs790056 (TT genotype and T allele) and LFA-1 rs8058823 (AA genotype and A allele) were found to be risk factors for CHD, whereas rare genotypes and alleles were found to be higher in healthy controls thus being protective.

G894T endothelial nitric oxide synthase polymorphism and ischemic stroke in Morocco.

Nitric oxide plays a major role in the regulation of cerebral blood flow and loss of its function leads to alteration of the vascular relaxation given its central role in the physiology of the vascular system. G894T eNOS polymorphism could have adverse effects on the expression and activity of endothelial nitric oxide synthase, which can result in functional impairment of the endothelium and contribute to the development of ischemic stroke in the different models of transmission. In this study, genotyping with PCR-RFLP and HRM (high resolution melting) methods were conducted on 165 ischemic stroke patients as well as 182 controls. The goal here was to compare genotyping with PCR-RLFP primer sequences of eNOS gene (size < 300 bp) to HRM. Our data suggests a statistically significant association between G894T eNOS polymorphism and ischemic stroke in recessive, dominant and additive models with P < 0.05 and odds ratio of 2.68 (1.08-6.70), 1.78 (1.16-2.73), and 1.71 (1.21-2.43) respectively. In sum, although the sample size is relatively small, it suggests that G894T eNOS polymorphism could be a potentially important genetic marker of ischemic stroke in the Moroccan population. Future studies should be conducted in this direction taking into consideration the functional activity of eNOS.

The association between polymorphism of P53 codon 72 Arg/Pro and hepatocellular carcinoma susceptibility: evidence from a meta-analysis of 15 studies with 3704 cases.

BACKGROUND: Emerging evidence has shown that p53gene participates in human carcinogenesis as tumor suppressors. Polymorphism of p53 gene codon 72 Arg/Pro (rs1042522) may influence the function of p53 protein and then affect the processing of carcinogenesis. It has been suggested that p53 codon 72 Arg/Pro polymorphism is associated with susceptibility to hepatocellular carcinoma (HCC). However, published results are inconsistent and inconclusive. To examine the validity of the association between the polymorphism and HCC risk, we performed this meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: We have conducted a search of case-control studies on the associations of p53 codon 72 polymorphism with susceptibility to HCC in PubMed, ScienceDirect, Bio-Med central, Springer-link, EBSCO, Wanfang databases and Chinese National Knowledge Infrastructure (CNKI) databases. A total of 15 studies were identified with 3704 cases and 4559 controls for codon 72 Arg/Pro polymorphism. The result did support a significant genetic association between Pro allele and susceptibility to HCC in all the genetic models. Similarly, subgroup analysis showed significant associations between the Arg/Pro polymorphism and susceptibility to HCC when stratifying by race, gender, source of controls and hepatitis virus infection status. CONCLUSIONS/SIGNIFICANCE: This meta-analysis suggests that p53 codon 72 Arg/Pro polymorphism may be associated with the risk of HCC, especially in subgroup analysis of Asian and Caucasian population, hospital-based population, the female, and the individuals infected with hepatitis virus. However, well-designed studies based on different ethnic groups with larger sample size and more detailed data are needed to confirm these conclusions.

Association of Interleukin-1ß and Gene Polymorphisms with Liver Pathogenesis in Hepatitis B Virus Infection among Eastern Indian Population.

BACKGROUND: Interleukin-1ß (IL-1ß) is an important member of the family of the proinflammatory cytokines that modulate outcome of hepatitis B virus (HBV) infection. OBJECTIVES: This study was designed to investigate the relationship between the polymorphic genotypes of the interleukin-1ß (IL-1ß) promoter region and the interleukin-1 receptor antagonist gene (IL-1RN) and disease outcome in HBV-infected individuals. METHODS: DNA was extracted from 395 study subjects including HBV carriers with varying clinical presentations, as well as healthy controls and spontaneously recovered cases (SRC). Polymorphisms in IL-1ß (at position -511) and IL-1RN (variable nucleotide tandem repeats, VNTR) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR based assay respectively. RESULTS: Among the study subjects, different IL-1ß (at position -511) (CC, CT and TT) and IL-1RN (1/1, 1/2, 2/2 and 1/3) polymorphic genotypes were found at variable proportions. Logistic regression analysis revealed, no notable difference at the level of IL-1ß promoter (P = 0.244; OR = 0.78; 95% CI = 0.52-1.18) or IL-1RN genotype polymorphism (P = 0.840; OR = 1.03; 95% CI = 0.78-1.36) among the HBV carriers and controls or SRC cases. Pairwise proportion testing showed, IL-1ß -511 genotype CC was significantly higher among asymptomatic carriers (ASC) in comparison with liver cirrhosis (LC) patients (P value = 0.028) and healthy control group (P-value = 0.036). IL-1RN genotype 2/2 was considerably higher in LC group than SRC as well as control group. Combinations of IL-1ß (-511) and IL-1RN polymorphisms were associated with disease progression, such as CC-1/2 with ASC and TT-2/2 with LC. CONCLUSION: IL-1ß polymorphisms are found to be associated with disease severity. Different polymorphic combinations are associated with degree of disease severity. Overall this is the first report from Eastern India, which shows association of IL-1ß polymorphisms with HBV-related hepatic complications.