Functional Single Nucleotide Polymorphisms (functional + single_nucleotide_polymorphism)

Distribution by Scientific Domains


Selected Abstracts


Interleukin-4 ,590 (C>T), toll-like receptor-2 +2258 (G>A) and matrix metalloproteinase-9 ,1562 (C>T) polymorphisms in pre-eclampsia

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 8 2008
R Fraser
Functional single nucleotide polymorphisms (SNPs) of interleukin (IL)-4 ,590 (C>T), toll-like receptor (TLR)-2 +2258 (G>A) and matrix metalloproteinase (MMP)-9 ,1562 (C>T) were examined by polymerase chain reaction,restriction fragment length polymorphism to identify their merit as genetic markers for pre-eclampsia. One hundred and seventeen pre-eclamptic women and 146 control subjects with uncomplicated singleton pregnancies participated in this study, conducted at Leeds General Infirmary and St James's University Hospital. While the TLR-2 +2258 (G>A) and MMP-9 ,1562 (C>T) SNPs failed to present any significant association with pre-eclampsia, there was a marked trend for an association between the IL-4 ,590 (C>T) SNP and pre-eclampsia (,2= 5.87, P = 0.055), with a prevalence of TT homozygous women in this group (OR 4.455, 95% CI 1.286,15.350). [source]


BDNF variant linked to anxiety-related behaviors

BIOESSAYS, Issue 2 2007
Kenji Hashimoto
Brain-derived neurotrophic factor (BDNF) is the most-abundant neurotrophin in the brain. In mammals, it is synthesized as a precursor called proBDNF, which is proteolytically cleaved to generate mature BDNF. The BDNF gene is located on chromosome 11p13, and a functional single nucleotide polymorphism (SNP) of this gene has been shown to produce a valine (Val)-to-methionine (Met) substitution in the proBDNF protein at codon 66 (Val66Met). Several papers suggest that this SNP is related to decreased hippocampal volume and hippocampus-mediated memory performance in humans. Recently, Chen et al.1 generated a variant BDNF mouse (BDNFMet/Met) that reproduces the phenotypic hallmarks in humans with a variant Met allele. In the behavioral analysis, BDNFMet/Met mice show increased anxiety-related behaviors. This mini-review examines the impact of Met substitution of proBDNF on anxiety-related behaviors. BioEssays 29: 116,119, 2007. © 2007 Wiley Periodicals, Inc. [source]


Association of FcGRIIa with Graves' disease: a potential role for dysregulated autoantibody clearance in disease onset/progression

CLINICAL ENDOCRINOLOGY, Issue 1 2010
Kadija Yesmin
Summary Objective, Although autoantibody production is a key feature of autoimmunity, it is not known whether variation in autoantibody production and clearance pathways is involved in disease susceptibility. The Fc Gamma Receptor IIa (FcGRIIa) molecule is involved in the clearance of autoantibodies and a functional single nucleotide polymorphism (SNP), rs1801274, which has been shown to alter autoantibody clearance, has been associated with a number of autoimmune diseases (AIDs) including systemic lupus erythematosus and type 1 diabetes. This study aimed to determine whether FcGRIIa is associated with Graves' disease (GD) in the UK Caucasian population by Tag SNP screening common polymorphisms within the FcGRIIa region. Design, A case control association study investigating nine Tag SNPs within FcGRIIa, which captured the majority of known common variation within this gene region. Patients, A dataset comprising 2504 UK Caucasian GD patients and 2784 geographically matched controls taken from the 1958 British Birth cohort. Measurements, We used the ,2 -test to investigate association between the Tag SNPs and GD. Results, Association between the rs1801274 (P,= 0·003, OR = 1·12 [95% CI = 1·03,1·22] and rs6427598 (P = 0·012, OR = 0·90 [95% CI = 0·83-0·98]) SNPs and GD was observed. No other SNPs showed association with GD. No associations were seen between any of the SNPs investigated and specific GD clinical phenotypes. Conclusions, This study suggests that variation in FcGRIIa predisposes to GD and further supports the role of FcGRIIa as a susceptibility locus for AIDs in general. [source]


Putative functional polymorphisms of MMP9 predict survival of NSCLC in a Chinese population

INTERNATIONAL JOURNAL OF CANCER, Issue 9 2009
Guangfu Jin
Abstract Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and their over-expression is often associated with unfavorable survival of non-small cell lung cancer (NSCLC). Because genetic variants can alter expression level or biological activity of MMPs, we hypothesized that potentially functional single nucleotide polymorphisms (SNPs) in key MMP genes may be associated with the survival of NSCLC patients. We selected and genotyped 14 putative functional SNPs in six MMP genes (MMP1, MMP2, MMP3, MMP7, MMP9 and MMP12) using PCR-RFLP methods in 561 NSCLC patients. Kaplan-Meier method with the log-rank test and Cox proportional hazard models were used for the survival analyses. The C-1562T, Arg279Gln and Arg668Gln polymorphisms in MMP9 were significantly associated with survival of patients with NSCLC (log-rank p values = 0.032, 0.038 and 0.036, respectively). The C-1562T and Arg668Gln loci were in complete linkage disequilibrium (r2 = 1). Patients carrying the 668Gln allele had improved survival with a median survival time (MST) of 51.6 months, compared with 21.8 months for those with the 668Arg/Arg genotype (log-rank p = 0.010). In contrast, the 279Gln/Gln genotype was associated with a significantly shortened MST (17.3 months, log-rank p = 0.030) in the recessive model. In the final multivariate Cox regression model, 279Gln/Gln was identified as an independent prognostic factor with an adjusted hazard ratio of 1.60 (95% confidence interval 1.07,2.41). The MMP9 Arg279Gln and Arg668Gln SNPs are potential predictors of survival in NSCLC patients. © 2008 Wiley-Liss, Inc. [source]


A nonsynonymous polymorphism in IL23R gene is associated with risk of gastric cancer in a Chinese population,

MOLECULAR CARCINOGENESIS, Issue 10 2010
Jianjian Chen
Abstract Interleukin-23 receptor (IL-23R) is a key element in T helper (Th)17 cell-mediated inflammatory process, which plays an important role in pathogenesis of gastric cancer. Genetic variants of IL-23R have been identified as the predisposing factors for immunopathologic process. In this study, we hypothesized that the functional genetic variants of IL-23R gene may modify the risk of gastric cancer. To test this hypothesis, we conducted a case,control study including 1043 gastric cancer patients and 1089 controls in a Chinese population to assess the association between two potentially functional single nucleotide polymorphisms (SNPs) rs6682925 T>C and rs1884444 T>G of IL-23R and risk of gastric cancer. We found that the variant allele (G) of rs1884444 T>G, with amino acid His substituted by Gln at codon 3, was significantly associated with a decreased risk of gastric cancer [adjusted allelic odds ratio (OR),=,0.78, 95% confidence interval (CI),=,0.68,0.88]. In the stratified analysis, we found that this protective effect of rs1884444 G allele was mainly evident in intestinal-type gastric cancer (adjusted allelic OR,=,0.75, 95% CI,=,0.65,0.87) other than in diffuse-type gastric cancer (adjusted allelic OR,=,0.96, 95% CI,=,0.76,1.22). However, we did not find any significant association of rs6682925 T>C with gastric cancer risk. These findings indicate, for the first time, that the nonsynonymous variant rs1884444 T>G of IL-23R may contribute to gastric cancer susceptibility, especially in intestinal-type gastric cancer, in Chinese population. © 2010 Wiley-Liss, Inc. [source]


A single nucleotide polymorphism in the alcohol dehydrogenase 7 gene (alanine to glycine substitution at amino acid 92) is associated with the risk of squamous cell carcinoma of the head and neck

CANCER, Issue 12 2010
Sheng Wei MD
Abstract BACKGROUND: The authors conducted a hospital-based study of 1110 patients with squamous cell carcinoma of the head and neck (SCCHN) and a control group of 1129 patients to replicate the associations reported by a recent, large European study between 2 potentially functional single nucleotide polymorphisms (SNPs) of the alcohol dehydrogenase (ADH) genes, a substitution in ADH1B at amino acid 48 from arginine to histidine (R48H) (reference SNP number [rs]1229984; guanine to adenine [G,A]) and a substitution in ADH7 at amino acid 92 from alanine to glycine (A92G) (rs1573496; cytosine to guanine [C,G]), and the risk of squamous cell carcinoma of the head and neck (SCCHN). METHODS: Multivariate logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). False-positive report probabilities (FPRPs) also were calculated for significant findings. RESULTS: The ADH7 A92G GG and combined CG + GG genotypes were associated with a decreased risk of SCCHN (GG: adjusted OR, 0.32; 95% CI, 0.13-0.82; CG + GG: adjusted OR, 0.74; 95% CI, 0.59-0.94; FPRP, .098) compared with the CC genotype. This association was also evident in subgroups of older patients (aged >57 years), men, former smokers, patients with oral cancer, and patients with N) lymph node status (P < .05 for all); however, such associations were not observed for the ADH1B R48H SNP. CONCLUSIONS: The current results support the ADH7 A92G SNP as a marker for the risk of SCCHN in non-Hispanic white populations. Cancer 2010. © 2010 American Cancer Society. [source]


Genetic variants in cell cycle control pathway confer susceptibility to bladder cancer

CANCER, Issue 11 2008
Yuanqing Ye PhD
Abstract BACKGROUND Cell cycle checkpoint regulation is crucial for the prevention of carcinogenesis in mammalian cells. METHODS To test the hypothesis that common sequence variants in the cell cycle control pathway may affect bladder cancer susceptibility, the effects of a panel of 10 potential functional single nucleotide polymorphisms (SNPs) from 7 cell cycle control genes, P53, P21, P27, CDK4, CDK6, CCND1, and STK15, were evaluated on bladder cancer risk in a case-control study of 696 bladder cancer cases and 629 healthy controls. RESULTS Overall, on individual SNP analysis only individuals with the p53 intron 3 16-bp duplication polymorphism variant allele had a significantly reduced bladder cancer risk (odds ratio [OR] = 0.74, 95% confidence interval [CI], 0.56,0.96). This effect was more evident in former smokers and younger subjects. We then applied the Classification and Regression Tree (CART) statistical approach to explore the high-order gene-gene and gene-smoking interactions. In the CART analysis, smoking status was identified as the most influential factor for bladder cancer susceptibility. The final decision tree by CART contained 6 terminal nodes. Compared with the second-lowest risk group the ORs for terminal nodes 1 and 3 to 6 ranged from 0.46 to 6.30. CONCLUSIONS These results suggest that cell cycle genetic polymorphisms may affect bladder cancer predisposition through modulation of host genome stability and confirm the importance of studying gene-gene and gene-environment interactions in bladder cancer risk assessment. Cancer 2008. © 2008 American Cancer Society. [source]