FAS Polymorphisms Research Articles

Intrinsic and Extrinsic Cell Apoptotic Pathways in Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis: A Systematic Review.

We aimed to verify the influence of intrinsic and extrinsic cell apoptotic pathways on the inhibition of cellular apoptosis in patients with tropical spastic paralysis/myelopathy related to human T cell lymphotropic virus type 1. The databases accessed were PubMed, Scopus, Science Direct, and Web of Science. Neither the time of publishing nor the language of the articles was limited. The descriptors used for this systematic literature review were: Tropical Paraparesis, Proto-Oncogenic Protein C, Bcl-2, Bcl-X Protein, Bax protein, Fas ligand (FasL) protein, Fas receptor, TNF-related apoptosis-inducing ligand and Fas-associated protein with death domain (FADD)-like apoptosis regulating. The search resulted in 546 articles from which 9 articles were selected for analysis; ranging from serum levels of Bcl-2, Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) measured by enzyme-linked immunosorbent assay and the levels of cellular expression of Bcl-2 and Bcl-xL the TCD4+ lymphocytes accessed by western blot. Most studies accessed either gene expression or polymorphism of Fas, FasL, and TRAIL in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), whereas one study used flow cytometry and fluorescence to determine Fas expression. Increased Bcl-xL expression inhibited T lymphocyte apoptosis, whereas Bcl-2, serum levels, and cellular expression did not influence T lymphocyte apoptosis and serum levels of Fas were significantly higher and associated with markers of leukocyte activation in patients with HAM/TSP. In addition, Fas polymorphism (FAS-670AA) was associated with higher proviral load. There is a need for additional research on this issue since the number of patients was small and the studies presented higher heterogeneity.

FAS and FASL polymorphisms and susceptibility to hepatitis B virus infection in Javanese individuals

Hepatitis B virus infection is still a major global health problem. The polymorphisms in FAS and FASL genes may involve with susceptibility to hepatitis B virus infection for Javanese. To investigate the association of FAS and FASL polymorphisms with the susceptibility to hepatitis B virus infection in Javanese individuals, blood samples with hepatitis B virus infection was subjected for polymerase chain reaction-restriction fragment length polymorphism to genotype the FAS-670 A/G and FASL -124A/G polymorphism status, respectively. The frequencies of G/G genotype and G allele of FAS gene in the hepatitis B virus-infected blood sample were higher than that of the healthy sample (OR 3.5, 95%CI: 1.658 - 7.390, p = 0.001 and OR 2.3, 95%CI: 1.352 - 3.779, p = 0.002, respectively). It is proposed that the hepatitis B virus infection outcome in Japanese individuals might be influenced by FAS-670 A/G polymorphism through alteration in apoptosis of hepatocytes.

Comments on: Gene Polymorphisms in FAS (Rs3740286 and Rs4064) are Involved in Endometriosis Development in Brazilian Women, but not those in CASP8 (rs13416436 and rs2037815).

Comments on: Gene Polymorphisms in FAS (Rs3740286 and Rs4064) are Involved in Endometriosis Development in Brazilian Women, but not those in CASP8 (rs13416436 and rs2037815).

Gene Polymorphisms in FAS (Rs3740286 and Rs4064) Are Involved in Endometriosis Development in Brazilian Women, but not those in CASP8 (rs13416436 and rs2037815).

The present study aims to investigate the association between caspase-8 (CASP8) (rs13416436 and rs2037815) and Fas cell surface death receptor (FAS) (rs3740286 and rs4064) polymorphisms with endometriosis in Brazilian women. In the present case-control study, 45 women with a diagnosis of endometriosis and 78 normal healthy women as a control group were included. The genotyping was determined by real-time polymerase chain reaction (PCR) with Taqman hydrolysis probes (Thermo Fisher Scientific, Darmstadt, Germany). Genotypic and allelic frequencies were analyzed using Chi-squared (χ2) test. In order to determine the inheritance models and haplotypes ,SNPStats (Institut Català d'Oncologia, Barcelona, Spain) was used. Levels of 5% (p = 0.05) were considered statistically significant. No significant difference was observed in genotypic or allelic frequencies between control and endometriosis groups for rs13416436 and rs2037815 (CASP8 gene). On the other hand, a significant difference between rs3740286 and rs4064 (FAS gene) was found. Regarding polymorphisms in the FAS gene, a statistically significant difference was found in co-dominant and dominant models. Only the haplotype containing the rs3740286A and rs4064G alleles in the FAS gene were statistically significant. The polymorphisms in the CASP8 gene were not associated with endometriosis. The results indicate an association between FAS gene polymorphisms and the risk of developing endometriosis.

Fas and FasL genetic polymorphisms in women with recurrent pregnancy loss: a case-control study

Aberrant apoptosis at the trophoblast–maternal interface and abnormal expression of Fas and Fas ligand (FasL) have been reported in complicated pregnancies with recurrent pregnancy losses (RPL) and preeclampsia. We assessed the prevalence of Fas and FasL genetic polymorphisms in Korean women with RPL and in fertile controls. In total, 306 women with RPL and 298 fertile controls were enrolled. Genotype distributions of Fas and FasL in RPL patients versus fertile controls were examined under the Hardy–Weinberg equilibrium. Fas −670 A/G genotype (AA versus AG versus GG, p = 0.340) and allele frequencies (A versus G, p = 0.412) were not different between the RPL and control groups. There was no difference in each Fas −1377 G/A and FasL −844 C/T genotype, and their allele frequencies. In addition, the unions of two zygosities of each genotype and their combined genotypes did not differ between two groups. No difference in the prevalence of Fas and FasL single-nucleotide polymorphisms (SNPs) was observed between women with RPL and fertile controls among Korean women. To determine the possibility of genetic polymorphisms in Fas and its ligand as risk factors for RPL, further studies in various races and a large study population are needed.

Single-Nucleotide Polymorphisms of FAS and FASL Genes and Risk of Idiopathic Aplastic Anemia

ABSTRACTFAS/FASL signaling system plays a vital role in the regulation of apoptosis, envisaged as a death process required for immune surveillance to prevent autoimmunity and tumorigenesis along with several other biological activities. Several single-nucleotide polymorphisms (SNPs) of FAS/FASL system can result in aberrant apoptosis, which can cause different cancers and autoimmune diseases. Aplastic anemia (AA) is an autoimmune dysfunction characterized by peripheral blood pancytopenia associated with hypoplasia of bone marrow. The aim of this study was to screen Pakistani AA patients and controls for two Fas SNPs rs2234767 and rs1800682 and two FASLG SNPs rs763110 and rs5030772. Genotyping of 392 DNA samples was done by Tetra-ARMS polymerase chain reaction. Genotypic frequencies of Fas rs1800682 and FASLG rs5030772 showed significance difference in their distribution in both controls and patients, while Fas rs2234767 and FASLG rs763110 SNPs had no such difference. Carriers of rs1800682 AG+GG had a very odd ratio of 4.63, with 95% confidence interval (CI) of 3.01–7.11, while individuals with FASLG rs5030772 AG+GG were more common in controls than patients with OR 0.53 and 95% CI of 0.34–0.83. Cumulative effects of these SNPs were analyzed, and they showed almost similar trends; however, Fas rs2234767 and FASLG rs763110 genotypes in combination with Fas rs1800682 and FASLG rs5030772 demonstrated significant association. This study provided information that endorsed the involvement of FAS/FASL system SNPs in the pathogenesis of AA; further studies should be designed to understand the exact role of SNPs that can help in early diagnosis and treatment.

FAS promoter polymorphisms and serum sFas level are associated with increased risk of nerve damage in Bangladeshi patients with Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system triggered by molecular mimicry between pathogen lipopolysaccharides and host nerve gangliosides. Polymorphisms in the Fas receptor (FAS) and Fas ligand (FASL) genes may potentially alter the elimination of autoreactive immune cells and affect disease susceptibility or disease severity in GBS. We detected single nucleotide polymorphisms (SNPs) in FAS (-1377G/A and -670A/G) and FASL (-843C/T) in a prospective cohort of 300 patients with GBS and 300 healthy controls from the Bangladeshi population. Genotype distributions were not significantly different between patients with GBS and healthy controls. The FAS -670 AG heterozygous (P = 0.0005, OR = 2.5, 95% CI = 1.5–4.2) and GG homozygous (P = 0.0048, OR = 2.6, 95% CI = 1.3–5.0) genotypes were more common in patients with anti-GM1 antibodies than patients without anti-GM1 antibodies. The FAS -670 G allele was more prevalent in anti-GM1 antibody-positive than -negative patients (P = 0.0002, OR = 1.9, 95% CI = 1.4–2.7) and also in patients with the axonal subtype than demyelinating subtype (P < 0.0001, OR = 4.8, 95% CI = 2.3–10.1). The 1377G/-670G GG haplotype was significantly associated with the axonal subtype (P < 0.0001) and anti-ganglioside antibody-positivity (P = 0.0008) in GBS. Serum sFas (237.5 pg/mL vs. 159.5 pg/mL; P < 0.0001) and sFasL (225.1 pg/mL vs. 183.4 pg/mL; P = 0.0069) were elevated in patients with GBS compared to healthy controls, and among patients with high serum sFas was associated with severe GBS (P = 0.0406). In conclusion, this study indicates FAS-FASL promoter SNPs may promote the production of cross-reactive anti-ganglioside antibodies in GBS.

Genetic polymorphisms of FAS and EVER genes in a Greek population and their susceptibility to cervical cancer: a case control study.

BackgroundThe aim of the study was to evaluate the association of two SNPs of EVER1/2 genes’ region (rs2290907, rs16970849) and the FAS-670 polymorphism with the susceptibility to precancerous lesions and cervical cancer in a Greek population.MethodsAmong the 515 women who were included in the statistical analysis, 113 belong to the case group and present with precancerous lesions or cervical cancer (27 with persistent CIN1, 66 with CIN2/3 and 20 with cervical cancer) and 402 belong to the control group. The chi-squared test was used to compare the case and the control groups with an allelic and a genotype-based analysis.ResultsThe results of the statistical analysis comparing the case and the control groups for all the SNPs tested were not statistically significant. Borderline significant difference (p value = 0.079) was only found by the allelic model between the control group and the CIN1/CIN2 patients’ subgroup for the polymorphism rs16970849. The comparison of the other case subgroups with the control group did not show any statistically significant difference.ConclusionsNone of the SNPs included in the study can be associated with statistical significance with the development of precancerous lesions or cervical cancer.

997P - Influence of FASL and FAS polymorphisms, enrolled in extrinsic apoptosis pathway, in the inherited increased risk of head and neck squamous cell carcinoma

Apoptosis plays an important role in origin of head and neck squamous cell carcinoma (HNSCC). Inherited genetic alterations, such as single nucleotide polymorphisms (SNPs), may influence the individual apoptotic capacity, having development of tumors as consequence. To the best of our knowledge, the roles of FASL c.-844C > T and FAS c.-671A > G SNPs in HNSCC risk, clinic pathological aspects and outcome are unclear, and therefore these were the aims of the present study. DNA of 463 patients and 470 controls were analyzed by PCR-RFLP. Patients were treated according to the Institutional protocol, including surgery, radio and chemotherapy. The statistical analyses were realized using chi-square, logistic regression model, multifactor dimensionality reduction (MDR), Kaplan-Meier, and univariate and multivariate Cox analyses. FASL TT genotype was more frequent in overall HNSCC patients (27.9% vs 16.2%, P= 0.001) and in those with SCC of oral cavity (30.0% vs 16.2%, P= 0.006), pharynx (29.9% vs 16.2%, P= 0.007), and larynx (25.4% vs 16.2%, P= 0.03) than in controls. Carriers of the genotypes were under a 3.24, 5.86, 2.93 and 2.54-fold increased risks of overall HNSCC and SCC of the mentioned subsites than others, respectively. An excess of FASL CT or TT plus FAS AA or AG combined genotype was seen in overall HNSCC patients compared to controls (91.1% vs 84.1%, P= 0.04); carriers of the genotype were under a 2.31-fold increased risk overall HNSCC than others. Among smokers, FASL TT and FAS AA genotypes were associated with 165.89 and 81.05-fold increased risks of HNSCC (P< 0.001), respectively. FASL c.-844C > T, FAS c.-671A > G SNPs and tobacco was the best interaction MDR model for risk of overall HNSCC and SCC of oral cavity, pharynx and larynx (P< 0.001). The median follow-up time of HNSCC patients was 46.0 months (1.6-166.0); no association of SNPs and patientś survival was seen in study. Our data present preliminary evidence that inherited abnormalities in FASL c.-844C > T and FAS c.-671A > G SNPs are determinants of overall HNSCC and SCC of oral cavity, pharynx and larynx, particularly among smokers, possibly due to their action in tumor carcinogenesis.

Association of FASL and FAS polymorphisms, enrolled in extrinsic apoptosis pathway, with head and neck squamous cell carcinoma risk and outcomes.

6053Background: Apoptosis plays an important role in origin of head and neck squamous cell carcinoma (HNSCC). Inherited genetic alterations, such as single nucleotide polymorphisms (SNPs), may infl...

Polymorphisms of extrinsic death receptor apoptotic genes (FAS -670 G>A, FASL -844 T>C) in coronary artery disease.

Apoptosis plays an important role in atherogenesis and rupture of vulnerable plaques in coronary artery disease. FAS and FAS ligand (FASL) induce apoptosis when FAS binds to FAS-L. However sFas blocks apoptosis by binding to FAS and FASL or sFasL. The present study is sought to examine the role of extrinsic apoptotic genes (FAS, FASL) polymorphism and serum levels of FAS, FASL in the pathogenesis and susceptibility to CAD in south Indian population. The study included 300 CAD patients and 300 healthy controls. Lipid profiles, sFas, sFasL were estimated by commercially available kits. FAS -670 G>A, FASL -844 T>C genotypes were analyzed by PCR-RFLP. Secondary structures of pre mRNA were analyzed by the Vienna RNA webserver and gene-gene and gene-environment interactions were determined by MDR analysis. Total cholesterol, triglyceride and LDL levels were significantly high in CAD patients compared to the controls. Molecular analysis revealed that the frequency of the AA genotype of FAS (54% vs 27%) and CC genotypes of FASL (10.3% vs 1.3%) were high in CAD patients compared to controls. Secondary structure analysis of FAS and FASL confirmed our molecular analysis. sFas levels were low while serum sFasL were high in CAD patients. MDR analysis revealed synergistic effects of gene polymorphisms and additive effects of epidemiological factors on risk of CAD. Polymorphisms of FAS (-670 G/A), FASL (-844 T/C) and their circulating levels play an important role in the pathology of CAD.

The Effects of Polymorphisms of Death Pathway Genes and Mitochondrial Pathway Genes in Intervertebral Disc Degeneration.

It has been proposed that apoptosis is effective on intervertebral disc degeneration. This study is the first study in which both polymorphisms and expressions of apoptotic genes in patients with intervertebral disc degeneration (IVDD) are evaluated together. The aim of our study is to determine whether polymorphisms and expressions of apoptotic genes involved in both pathways are related with grades of IVDD or not. Blood and tissue samples of 100 patients diagnosed with lumbar disc degeneration were collected. Patients were divided into 2 groups according to their radiological degeneration grades; grade 2 (mild), and grade 3 and 4 (severe). Polymorphisms in Fas (rs 2234767), Bcl-2 (rs 1801018) and Bax (rs 4645878) genes were determined with real-time PCR. Expressions of these genes were analyzed immunohistochemically following histological degeneration scoring. Whereas no relationship was found among polymorphisms of Fas and Bax genes and their expressions, we have determined a relationship among GG genotype of Bcl-2 and their expressions. Additionally, the ratio of Bax-positive cells was related with IVDD grades. Moreover, radiological degeneration grades were compatible with histological degeneration scores. GG genotype of Bcl-2 gene may influence the level of its expression and may be effective on the development of IVDD. Additionally, expression of Bax gene may be related with different grades of IVDD.

Fas-670A>G polymorphism is not associated with an increased risk of acute myeloid leukemia development.

The association between the increased risk of acute myeloid leukemia (AML) and Fas promoter polymorphisms has been reported previously; however, the results are inconclusive. The present study performed one case-control study to investigate the association, and a total of 98 AML patients and 2,014 healthy controls were genotyped. The data showed that the distribution of Fas-670AA, GA and GG genotypes among the AML patients were not significantly different from those of the healthy controls, all P>0.05. Following this a sub-study was conducted to analyze individuals who neither smoked nor drank. The results demonstrated that there was still no significant association between the Fas-670 polymorphism and risk of AML development, all P>0.05. Furthermore, in order to address a more accurate estimation of the association, a meta-analysis was conducted. Data were systematically collected from the Pubmed, EMBASE and the Wanfang Library. A total of 3 studies were included in this meta-analysis, which contained 1,144 AML cases and 3,806 controls. No significant association was detected between the Fas-670A>G polymorphism and AML risk [GA+GG vs. AA: odds ratio (OR) 0.93; 95% confidence interval (CI), 0.79–1.09; GG vs. AA: OR, 1.01; 95% CI, 0.82–1.24; GA vs. AA: OR, 1.12; 95% CI, 0.94–1.32; GG vs. AA+GA: OR, 0.94; 95% CI, 0.79–1.12; G vs. A: OR, 1.01; 95% CI, 0.91–1.12; all P>0.05). The analysis clearly indicated that there was no significant connection between the Fas-670A>G polymorphism and the increased risk of AML.

Identification of Single Nucleotide Polymorphism Marker and Association Analysis of Marbling Score in Fas Gene of Hanwoo.

The Fas (APO-1, TNFRSF6) gene known as a member of the tumor necrosis factor receptor superfamily was selected for DNA marker development in Korean cattle. It is a cell membrane protein and mediates programmed cell death (apoptosis). We discovered single nucleotide polymorphisms (SNPs) within Fas gene in order to develop novel DNA markers related to economical traits at the genomic level. The sequences of whole exon and 1 kb range of both front and back of the gene were determined by direct-sequencing methods using 24 cattle. A total of 55 SNPs were discovered and we selected 31 common polymorphic sites considering their allele frequencies, haplotype-tagging status and linkage disequilibrium (LD) for genotyping in larger-scale subjects. The SNPs were confirmed genotype through the SNaPshot method (n = 274) and were examined for a possible genetic association between Fas polymorphisms and marbling score. So, the SNPs that were identified significant are g.30256G>C, g.31474C>A, g.31940A>G, and g.32982G>A. These results suggest that SNPs of Fas gene were associated with intramuscular fat content of meat quality traits in Korean cattle.

Associations between single nucleotide polymorphisms in the FAS pathway and acute kidney injury.

IntroductionTo determine whether single nucleotide polymorphisms (SNPs) in FAS and related genes are associated with acute kidney injury (AKI) in patients with acute respiratory distress syndrome (ARDS).MethodsWe studied 401 (Caucasian N = 310 and African-American N = 91) patients aged ≥ 13 years with ALI who enrolled in the Fluid and Catheter Treatment Trial (FACTT) between 2000 and 2005 from 20 North American centers. We genotyped 367 SNPs in 45 genes of the Fas/Fas ligand pathway to identify associations between SNPs in Fas pathway genes and the development of AKI by day 2 after enrollment in FACTT, adapting Acute Kidney Injury Network (AKIN) criteria. Written informed consent was obtained from participants or legally authorized surrogates in the original FACTT study and available to use for secondary analysis.ResultsIn Caucasian patients, we identified associations between two SNPs and the incidence of AKI (stage 1 and above): rs1050851 and rs2233417; both are found within the gene for nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (NFKBIA). For rs1050851 and rs2233417, the odds ratios (ORs) were 2.34 (95 % confidence interval (CI) = 1.58–3.46, p = 1.06 × 10−5, FDR = 0.003) and 2.46 (CI = 1.61–3.76, p = 1.81 × 10−5, FDR = 0.003) for each minor allele, respectively. The associations were stronger still for AKIN stage 2–3 with respective ORs 4.00 (CI = 2.10–7.62, p = 1.05 × 10−5, FDR = 0.003) and 4.03 (CI = 2.09–7.77, p = 1.88 × 10−5, FDR = 0.003) for each minor allele homozygote. We observed no significant association between these SNPs and AKI in the smaller subset of African Americans.ConclusionIn Caucasian patients with ALI, the presence of minor alleles in two SNPs in NFKBIA was strongly associated with the development of AKI.Trial registrationNCT00281268. Registered 20/01/2006.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-1084-5) contains supplementary material, which is available to authorized users.

Association of promoter polymorphisms of Fas -FasL genes with development of Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is a monoclonal myeloproliferative disorder of hematopoietic stem cells (HSCs), characterized by reciprocal translocation, leading to the formation of BCR-ABL oncogene with constitutive tyrosine kinase (TK) activity. This oncogene is known to deregulate different downstream pathways which ultimately lead to cell proliferation, defective DNA repair, and inhibition of apoptosis. Fas (Fas cell surface death receptor) is a member of tumor necrosis factor (TNF) superfamily which interacts with its ligand, FasL, to initiate apoptosis. Promoter polymorphisms in Fas-FasL genes are known to influence the apoptotic signaling. Hence, the present study has been aimed to find out the association of the promoter polymorphisms in Fas and FasL genes with the development and progression of CML. Blood samples from 772 subjects (386 controls and 386 cases) were collected and genotyped for Fas-FasL gene polymorphisms through PCR-RFLP method. The association between SNPs and clinical outcome was analyzed using statistical softwares like SPSS version 20, SNPSTATs, and Haploview 2.1. The study revealed a significant association of Fas -670 G>A and FasL -844 T>C polymorphisms with the development of CML while Fas -670 AG was associated with accelerated phase. Combined risk analysis by taking the risk genotypes in cases and controls revealed a significant increase in CML risk with increase in number of risk genotypes (one risk genotype-OR 1.99 (1.44-2.76), p < 0.0001; two risk genotypes-OR 3.33 (1.91-5.81), p < 0.0001). Kaplan-Meier survival analysis of Fas -670 A>G and FasL -844 T>C showed reduced event-free survival in patients carrying the variant genotypes, Fas -670 GG, 32.363±6.33, and FasL -844 CC, 33.489±5.83, respectively. Our findings revealed a significant association of Fas -670 GG, FasL -844 TC, and CC genotypes with increased risk of CML.

OP0015 Polymorphisms in apoptosis-related genes and risk of HPV-mediated cervical cancer: A case-control study

Background Evasion of apoptosis is a hallmark of cancer. Genetic polymorphisms in apoptosis-related genes can potentially alter apoptotic efficacy, which in turn influence risk of cancer. In this study, we investigated the association of three apoptosis-related genetic polymorphisms, namely FAS −670A>G, p53 codon 72, and MDM2 309T>G polymorphisms with HPV-mediated cervical cancer risk in the multiethnic Malaysian population. Methods 95 patients with histopathologically confirmed cervical cancer and 95 cancer-free healthy females were recruited into this case-control study. HPV types were determined by use of flow-through hybridisation technique. The polymorphisms were genotyped with the PCR-RFLP method. Logistic regression analysis was performed to measure the risk association present. Findings Variant genotypes of FAS and MDM2 polymorphisms were associated with increased cervical cancer risk (odds ratio (OR) 3.360, 95% confidence interval (CI) 1.494–7.556, p = 0.003 and OR 3.381, 95% CI 1.521–7.512, p = 0.003, respectively). The association of the FAS variant genotype was only significant among participants of Malay ethnicity (OR 5.377, 95% CI 2.085–13.865, p = 0.001), whereas significance of the MDM2 polymorphism was not observed in all ethnic groups. When stratified by patient HPV type, the association of the FAS polymorphism remained significant only in cervical cancers mediated by HPV16 (OR 3.333, 95% CI 1.127–9.863, p = 0.030) and ‘other’ HPV types (OR 6.00, 95% CI 1.565–23.007, p = 0.009), whereas MDM2 polymorphism remained significant only in HPV16-mediated cancer (OR 4.740, 95% CI 1.525–14.729, p = 0.007). Significant associations were also observed for various FAS -p53 and FAS - MDM2 , but not p53- MDM2 , combination genotypes. Interpretation FAS −670A>G and MDM2 309T>G polymorphisms could play a role in modulating cervical cancer risk among Malaysian women. This study is being continued with a larger sample size.

Association between the CTLA-4, CD226, FAS polymorphisms and rheumatoid arthritis susceptibility: A meta-analysis

ObjectiveWe explored whether cytotoxic T lymphocyte antigen-4 (CTLA-4) rs5742909, CD226 rs763361, FAS rs1800682, and FASL rs763110 polymorphisms are associated with rheumatoid arthritis (RA). MethodsWe performed a meta-analysis on the association between the four gene polymorphisms and RA. ResultsNineteen studies were included in the meta-analysis. Meta-analysis of all study subjects showed no association between RA and the CTLA-4 rs5742909 T allele (OR=1.057, 95% CI=0.782–1.429, p=0.719). However, the meta-analysis revealed an association between RA and the CD226 rs763361 T allele in all study subjects (OR=1.294, 95% CI=1.063–1.576, p=0.010), and an association was found between the CD226 rs763361 TT genotype and RA in Asians (OR=1.363, 95% CI=1.126–1.651, p=0.001). Meta-analysis showed no association between RA and the FAS rs1800682 G/A polymorphism. However, meta-analysis revealed an association between RA and the FASL rs763110 T allele in all study subjects (OR=1.366, 95% CI=1.093–1.707, p=0.006) and in Asians (OR=1.402, 95% CI=1.059–1.855, p=0.014). ConclusionsOur meta-analysis demonstrates that the CD226 rs763361 and FASL rs763110 polymorphisms are associated with RA, especially in Asians.

Fas –FasL genotype and phenotype in preeclampsia

Fas –FasL genotype and phenotype in preeclampsia

The diplotype Fas -1377A/-670G as a genetic marker to predict a lower risk of breast cancer in Chinese women.

This study was designed to reveal the effects of Fas and FasL polymorphisms of interest on breast cancer risk. A total of 439 patients with breast cancer and 439 controls were enrolled in this study. The genotypes Fas -1377G/A, Fas -670A/G, and FasL -844 T/C were detected by MassARRAY. The protein expressions of estrogen receptor, progesterone receptor, and CerbB-2 were determined by immunohistochemistry. Among the 439 patients, Fas mRNA levels in 22 samples of breast cancer and adjacent normal tissues were detected by real-time polymerase chain reaction, and the soluble Fas and Fas ligand concentrations of 180 patients were measured by enzyme-linked immunosorbent assay. The Fas -1377GA, Fas -1377AA, Fas -670AG, Fas -670GG, and FasL -844TC genotypes were associated with a reduced risk of breast cancer. Haplotype analysis indicated that Fas -1377G/-670A was associated with an increased risk of breast cancer, whereas Fas -1377A/-670A was associated with the opposite effect. Furthermore, gene-gene interaction analysis revealed that the Fas -1377GA/AA (-670AG/GG) and FasL -844CC or TC/TT genotypes were associated with a decreased risk of breast cancer. Meanwhile, -1377GG and -670AA genotypes were associated with higher soluble Fas concentrations than other genotypes. We conclude that Fas and FasL polymorphisms can affect breast cancer risk and that Fas polymorphisms are likely to affect breast cancer risk by regulating the soluble Fas concentration.