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At least 973 records · Page 54Linked to original sources
PubMed2006

Correlation between single nucleotide polymorphisms in a calprotectin subunit gene and risk of periodontitis in a Chinese population.

S100A8, the light subunit of calprotectin, has been known to be associated with periodontal inflammation. The present study looked to detect whether three polymorphisms in the upstream region of the S100A8 gene are correlated with periodontitis. Three hundred and twenty one subjects, including chronic periodontitis (CP) patients, aggressive periodontitis (AgP) patients and periodontally healthy controls, were recruited. The SNPs rs3795391, rs3806232 and rs3885688 were analyzed by PCR-RFLP analysis. No person carried the rs3885688 polymorphism in this cohort. For the other two polymorphisms, the combined effects of genotype/allele and gender were shown to be associated with the risk of periodontitis using multivariate logistic regression analysis. The G+ genotype/G allele may be considered to exert a significant protective effect in males against AgP (Genotype: rs3795391: P= 0.032, rs3806232: P= 0.017; Allele: rs3795391: P= 0.024, rs3806232: P= 0.013). Although the combined effects of genotype and gender on CP susceptibility were not observed for these two polymorphisms, there does seem to be increased risk of CP in males with allele A compared to females with allele A (rs3795391: P= 0.008; rs3806232: P= 0.009). Hence we found an important association between polymorphisms in the S100A8 gene and periodontitis in a Chinese population.

Adult↗
PubMed2005

Rapid determination of trisomy 21 from amniotic fluid cells using single-nucleotide polymorphic loci.

OBJECTIVES: Rapid detection of trisomy 21 is an important goal for prenatal genetic centers. Fluorescent-PCR and DNA fragment analysis was developed a decade ago and thousands of samples were analyzed in routine practice using this method. Quantitative real-time PCR with melting curve analysis using SNP markers for trisomy 21 detection was described recently. We studied the reliability of this method on a cohort of samples of Hungarian patients. METHODS: DNA was isolated with silica adsorption method from amniotic fluid cells. We investigated 67 trisomy 21 and 62 diploid samples in the study. Quantitative real-time PCR was performed using hybridization probes combined with melting curve analysis. Peak areas under the derivative curves were determined and analyzed. RESULTS: The SNP marker WIAF 899 was informative in 41.86% of cases and WIAF 2643 in 48.83%. The melting curve area ratios were significantly different between trisomic and normal cases for WIAF 899 (trisomic 0.5246 +/- 0.2498 vs 0.8347 +/- 0.5234; p < 0.001), while in the case of WIAF 2643, they were not different. CONCLUSION: Combined and selected SNP markers could be valuable tools for rapid trisomy 21 detection in prenatal genetic screening.

Alleles↗
PubMed2001

Frequency and distribution in three ethnic populations of single nucleotide polymorphisms in the MICA gene.

The Homo sapiens major histocompatibility complex (MHC) class 1 chain related gene A (MICA) was scanned for novel single nucleotide polymorphisms (SNPs) using a panel of DNA samples from African-, Japanese- and Mexican-Americans. Overlapping primer-pairs were used to amplify products in the size range of 300 to 400 bp that were sequenced and scanned for SNPs using Phred, Phrap, Polyphred and Consed sequence analysis programs. A total of 16 SNPs were detected, six of which represent new variant nucleotides in the Homo sapiens MICA gene. Three of the variants also represent amino acid changes in the MICA protein. Differences among the three ethnic panels in the frequency of the variant nucleotides observed were inconsistent, but significant for seven of the SNPs detected. Though a small sample size, this study represents the first multi-population based analysis of the frequency and distribution of SNPs in the MICA gene, a locus that may be essential in the antigenic recognition by gammadelta T cells.

Alleles↗
PubMed1999

Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism.

The human MTH1 gene for 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase, produces seven types (types 1, 2A, 2B, 3A, 3B, 4A and 4B) of mRNAs. The B-type mRNAs with exon 2b-2c segments have three additional in-frame AUGs in their 5' regions. We report here that these transcripts produce three forms of MTH1 polypeptides (p22, p21 and p18) in in vitro translation reactions. Three polypeptides were also detected in extracts of human cells, using western blotting. B-type mRNAs with a polymorphic alteration (GU-->GC) at the beginning of exon 2c that converts an in-frame UGA to CGA yielding another in-frame AUG further upstream, produced an additional polypeptide (p26) in vitro. Substitution of each AUG abolished the production of each corresponding polypeptide. Cell lines from individuals with the GC allele contain more B-type mRNAs than do those of GT homozygotes, and the former produce all of four polypeptides but the latter lack p26. Amounts of each polypeptide reflected copy number of the GC allele in each cell line. There is an apparent linkage dis-equilibrium between the two polymorphic sites, GT/GC at exon 2c and Val83/Met83 at codon 83 for p18.

Base Sequence↗
PubMed2002

Influence of vascular endothelial growth factor single nucleotide polymorphisms on tumour development in cutaneous malignant melanoma.

Vascular endothelial growth factor (VEGF) is a potent regulator of vasculogenesis and tumour angiogenesis. We have investigated whether the VEGF -2578, -1154, +405 and +936 SNPs and associated haplotypes confer susceptibility to and/or influence prognosis in cutaneous malignant melanoma (CMM) skin cancer. A total of 152 CMM patients and 266 controls were genotyped for VEGF promoter SNPs by ARMS-PCR. Strong linkage disequilibrium between the -2578, -1154 and +405 SNPs was detected (association, rho = 0.488-0.965), but not between these SNPs and SNP +936 (association, rho = 0.004-0.130). No SNPs or three SNP haplotypes (-2578, -1154, +405) were significantly associated with CMM, although a number of non-significant trends were observed. However, the VEGF -1154 AA genotype and -2578, -1154, +405 CAC haplotype were both significantly associated with less advanced (Stage 1) disease (P = 0.03). In addition, the VEGF -1154 AA genotype was associated with thinner primary vertical growth phase tumours (P = 0.002), while VEGF -1154 GG was associated with thicker primary tumours (P = 0.02). These preliminary results indicate that VEGF genotype may influence tumour growth in CMM, possibly via the effects of differential VEGF expression on tumour angiogenesis.

Endothelial Growth Factors↗
PubMed2005

A single-nucleotide polymorphism in the gene encoding lymphoid protein tyrosine phosphatase (PTPN22) confers susceptibility to generalised vitiligo.

Vitiligo is an acquired hypomelanotic skin disorder resulting from the loss of functional melanocytes from the cutaneous epidermis and autoimmunity has been suggested to play a part in its pathogenesis. Recently, the missense R620W polymorphism in the PTPN22 gene, which encodes lymphoid protein tyrosine phosphatase (LYP), has been associated with susceptibility to autoimmune disorders. The objective of this study was to ascertain if the disease-associated 1858T allele was also associated with generalised (nonsegmental) vitiligo and so the frequencies of the PTPN22 1858C/T alleles were investigated in 165 English patients with generalised vitiligo and 304 ethnically matched control subjects. The results indicated that the 1858T allele was significantly over-represented in the vitiligo patient group compared with the control cohort. Of 330 vitiligo alleles, 48 (14.5%) encoded the Trp620 variant compared to 52 of 608 (8.6%) control alleles (P=0.006; odds ratio=1.82, 95% confidence interval=1.17-2.82). The results indicate that the LYP missense R620W polymorphism may have an influence on the development of generalised vitiligo and provide further evidence for autoimmunity as an aetiological factor with respect to this disease.

Adult↗
PubMed2005

No association between the putative functional ZDHHC8 single nucleotide polymorphism rs175174 and schizophrenia in large European samples.

BACKGROUND: It has been recently reported that a functional variant in the ZDHHC8 gene encoding a putative palmitoyltransferase directly confers susceptibility to schizophrenia in females (). METHODS: We investigated the putative risk allele (rs175174) in four schizophrenia association samples including a Bulgarian proband and parent sample (474 trios) and three case-control panels of European origin (1028 patients/1253 control subjects) in an attempt to replicate these findings. RESULTS: Our results do not support the hypothesis that genetic variation at rs175174 is associated with increased risk for schizophrenia nor do they suggest the presence of gender-specific differences. CONCLUSIONS: Our data suggest that the reported genetic association by either represents type I error resulting from sampling variance or that rs175174 is in linkage disequilibrium (LD) with the functional variant for schizophrenia and different LD patterns obscure the detection of association.

Acyltransferases↗
PubMed2003

Selection of minimum subsets of single nucleotide polymorphisms to capture haplotype block diversity.

We present a simple numerical algorithm to select the minimal subset of SNPs required to capture the diversity of haplotype blocks or other genetic loci. This algorithm can be used to quickly select the minimum SNP subset with no loss of haplotype information. In addition, the method can be used in a more aggressive mode to further reduce the original SNP set, with minimal loss of information. We demonstrate the algorithm performance with data from over 11,000 SNPs with average spacing of 6 to 11 Kb, across all the genes of chromosomes 6, 21, and 22, genotyped on DNA samples of 45 unrelated African-Americans and 45 Caucasians from the Coriell Human Diversity Collection. With no loss of information, we reduced the number of SNPs required to capture the haplotype block diversity by 25% for the African-American and 36% for the Caucasian populations. With a maximum loss of 10% of haplotype distribution information, the SNP reduction was 38% and 49% respectively for the two populations. All computations were performed in less than 1 minute for the entire dataset used.

Algorithms↗
PubMed2004

Cholesteryl ester transfer protein promoter single-nucleotide polymorphisms in Sp1-binding sites affect transcription and are associated with high-density lipoprotein cholesterol.

Genetic variation in the human cholesteryl ester transfer protein (CETP) promoter has been shown to be associated with high-density lipoprotein cholesterol (HDL-C) levels and cardiovascular disease. Some of this variation occurs in Sp1/Sp3 binding sites in the proximal promoter. We find that both the known promoter polymorphism at -629 and the previously uncharacterized polymorphism at -38 are associated with HDL-C levels in vivo and affect transcription in vitro. While the -629 polymorphism is common in all ethnic groups, the -38 polymorphism is found at significant levels (6.4%) only among African Americans. Those homozygous for the less common -38A allele have higher HDL-C levels than those with the more frequent -38G allele. This association was found in a population of African Americans at risk of cardiovascular disease and then replicated in a different population chosen from among patients with extremes of HDL-C. When studied in vitro, the most transcriptionally active allele (-629C/-38G) yields 51% more reporter protein than the least active allele (-629A/-38A) in HepG2 cells. These transcriptional effects reflect the projected impact of increased CETP expression on HDL-C phenotypes seen in vivo.

Black or African American↗
PubMed2001

Association of single nucleotide polymorphisms in the interleukin-4 gene and interleukin-4 receptor gene with Crohn's disease in a British population.

Interleukin-4 (IL-4) is an important cytokine in mucosal immunity and plays a critical role in the development of colitis in T-alpha cell receptor mutant mice. Functionally significant polymorphisms have been described in the genes encoding IL-4 and IL-4 receptor. To examine the role of these polymorphisms in disease susceptibility 98 patients with ulcerative colitis, 86 patients with Crohn's disease and 321 healthy controls were genotyped for polymorphisms at position -34 in the IL-4 gene and codon 576 in the IL-4 receptor gene. Thirty-two percent of patients with Crohn's disease carried one or two copies of the variant allele for IL-4 compared with 16% of the controls (P = 0.002). Forty-one percent of patients with Crohn's disease carried one or two copies of the variant IL-4 receptor allele compared with 31% of the controls (P = 0.09). Fifteen percent of patients with Crohn's disease carried combination of both (IL-4 and IL-4 receptor) variant alleles compared with 4% of the controls (P = 0.005). Association with alleles resulting in high IL-4 transcription and enhanced signalling activity suggests that IL-4 may have a role in the pathogenesis of Crohn's disease.

Base Sequence↗
PubMed2006

Single nucleotide polymorphism in the promoter region of the lactoferrin gene and its associations with milk performance traits in Polish Holstein-Friesian cows.

Bovine lactoferrin (LTF) is a multifunctional small glycoprotein found in milk acting mainly as a defense factor in the mammary gland. Many polymorphisms have been found in the bovine LTF gene but almost none were considered as genetic markers of production traits in dairy cattle. In this study, the promoter fragment of LTF gene containing mutation (G/C) in position +32 has been amplified by PCR followed by genotyping by the SSCP and RFLP method. 358 Polish Holstein-Friesian cows were screened, giving the following frequency of genotypes: 0.628, 0.313 and 0.059 for GG, GC and CC, respectively. GLM (General Linear Model) analysis was applied to evaluate the associations of lactoferrin with milk performance traits, including SCC - somatic cell count. It was found that CC cows show significantly higher (P < or = 0.01) protein content in milk in comparison with GG cows. The values of other milk performance traits were also higher but at non-significant levels. SCC in milk was the lowest in CC cows, but also at a non-significant level.

Animals↗
PubMed2003

[Relation between single nucleotide polymorphism in estrogen-metabolizing genes COMT, CYP17 and breast cancer risk among Chinese women].

OBJECTIVE: To test the hypothesis whether polymorphism in estrogen-metabolizing genes, COMT and CYP17, impacts on the risk of breast cancer among Chinese women. METHODS: COMT (Val158Met) and CYP17 (T1931C) polymorphisms were detected by PCR-based restriction fragment length polymorphism analysis in 250 breast cancer patients and 250 frequency-matched normal controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression. RESULTS: COMT Met/Met genotype was found in 10.4% of breast cancer patients, which was significantly higher (P = 0.03) than that in controls (5.2%). Women with Met/Met genotype showed 2-fold increased risk for breast cancer (adjusted OR 2.1, 95% CI 1.1 - 4.5) compared with those with Val/Val or Val/Met genotypes. Stratified analysis showed that the elevated risk of breast cancer, associating with the COMT Met/Met genotype, was evident only among premenopausal women (adjusted OR 4.1, 95% CI 1.2 - 17.3) but not among postmenopausal women (adjusted OR 1.3, 95% CI 0.5 - 3.5). There was no significant difference in the distribution of CYP17 genotypes between breast cancer patients and the control subjects (P = 0.83). CONCLUSION: The allele encoding for low activity COMT, but not CYP17, may be a genetic risk factor for breast cancer among Chinese women.

Adult↗
PubMed2005

Epistatic effect of C-reactive protein (CRP) single nucleotide polymorphism (SNP) +1059 and interleukin-1B SNP +3954 on CRP concentration in healthy male blood donors.

Baseline C-reactive protein (CRP) concentrations are indicative of persons prone to cardiovascular diseases and are about 40-50% heritable. We have previously shown that interleukin (IL)-1B +3954 allele T is associated with lower CRP concentration. In this study, we aimed to examine the effect of this polymorphism together with the CRP +1059 gene polymorphism on baseline CRP concentrations, and genotyped 336 healthy blood donors for CRP +1059 (G-->C) and IL-1B +3954 (C-->T) polymorphisms. In men, the carriers of the CRP +1059 C-allele had significantly lower CRP values than GG homozygotes (0.66 versus 0.43 mg l(-1), up to -35%, P = 0.009). No significant difference was found in women. When the data were stratified for both of these polymorphisms in men, CRP +1059 GG homozygotes had low CRP concentrations only if they were allele-T carriers of IL-1B +3954 simultaneously (0.93 versus 0.50 mg l(-1), P = 0.013). Genotype CRP +1059 GG/IL-1B +3954 CC was associated with an almost 3-fold risk of a higher baseline CRP value [odds ratio (OR) 2.84 (CI 1.03-6.07)]. Thus, both IL-1B +3954 (C-->T) and CRP +1059 (G-->C) polymorphisms influence baseline CRP values and act independently of each other in male subjects. These polymorphisms might be predictive markers of persons prone to cardiovascular diseases.

Blood Donors↗
PubMed2004

Method for determination of (-102C>T) single nucleotide polymorphism in the human manganese superoxide dismutase promoter.

BACKGROUND: Manganese superoxide dismutase (MnSOD) plays a critical role in the detoxification of mitochondrial reactive oxygen species constituting a major cellular defense mechanism against agents that induce oxidative stress. The MnSOD promoter contains an activator protein-2 (AP-2) binding site that modifies transcription of MnSOD. Mutations have been identified in the proximal region of the promoter in human tumor cell lines. One of these mutations (-102C>T) has been shown to change the binding pattern of AP-2 leading to a reduction in transcriptional activity. The aim of our study was to develop a method to identify and determine the frequency of this (-102C>T) polymorphism in human tissues. RESULTS: A new TaqMan allelic discrimination genotype method was successfully applied to genomic DNA samples derived from blood, buccal swabs, snap frozen tissue and paraffin blocks. The polymorphism was shown to be in Hardy-Weinberg Equilibrium in an evaluation of 130 Caucasians from Warsaw, Poland: 44 (33.8%) were heterozygous and 6 (4.6%) were homozygous for -102T. CONCLUSION: This report represents the first description of the MnSOD -102C>T polymorphism in human subjects by a novel Taqman allelic discrimination assay. This method should enable molecular epidemiological studies to evaluate possible associations of this polymorphism with malignancies and other diseases related to reactive oxygen species.

Binding Sites↗
PubMed2002

SNPkit: an efficient approach to systematic evaluation of candidate single nucleotide polymorphisms in public databases.

There is widespread interest in devising genotyping methods for SNPs that are robust, inexpensive, and simple to perform. Although several high-throughput SNP genotyping technologies have been developed, including the oligonucleotide ligation assay, real-time PCR, and mass spectrometry, the issues of simplicity and cost-effectiveness have not been adequately addressed. Here we describe the application of a novel computer software package, SNPkit, which designs SNP genotyping assays based on a classical approach for discriminating alleles, restriction enzyme digestion. SNPkit can be used in genotyping assays for almost any SNPs including those that do not alter "natural" restriction sites. Using this method, 164 SNPs have been evaluated in DNA samples from 48 immortalized cell lines of randomly selected Chinese subjects. Sixty-two (37.8%) of the SNPs appeared to be common (frequencies of the minor alleles are > or = 5%) and were subsequently applied to a larger population-based sample. Overall, by using SNPkit, we have been able to validate and genotype accurately a large fraction of publicly available SNPs without sophisticated instrumentation.

Algorithms↗
PubMed2004

A single nucleotide polymorphism -1131T>C in the apolipoprotein A5 gene is associated with an increased risk of coronary artery disease and alters triglyceride metabolism in Chinese.

The disorder of triglyceride (TG) metabolism leading to hypertriglyceridemia is an independent risk factor for coronary artery disease (CAD). Variants in the newly identified apolipoprotein APOA5 gene were found to be strongly associated with elevated TG levels in different racial groups. In this study, we investigated the phenotypic effects of two polymorphisms (APOA5-1131T>C and APOC3-482C>T) on susceptibility to CAD in 312 Chinese CAD patients diagnosed by angiography. The frequency of the APOA5-1131C allele in these patients was significantly higher than that of the control group (39.9 vs. 33.3%, P=0.02). Compared with the wild type TT, CC homozygotes had a significantly increased CAD risk (OR=1.93 and OR=1.80 using unadjusted and adjusted logistic regression models, respectively). This association still existed after adjustment for the APOC3-482 variant. The APOA5-1131C allele also showed a correlation with increasing plasma TG levels (P<0.001). These data suggest that the APOA5-1131T>C polymorphism might contribute to an increased risk of CAD among Chinese as a result of its effect on TG metabolism; this effect was found to be independent of the APOC3-482C>T variant.

Apolipoprotein A-V↗
PubMed2006

A single nucleotide polymorphism in CHAT influences response to acetylcholinesterase inhibitors in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a devastating neurodegeneration with a characteristic deficit in cholinergic neurotransmission. Treatment with acetylcholinesterase (AChE) inhibitors aims to reverse this deficit and does ameliorate the decline in cognition in some AD patients, although response is variable. OBJECTIVE: To examine whether sequence variation in the gene encoding choline acetyltransferase (CHAT), which encodes the major catalytic enzyme of the cholinergic pathway, predicts response to AChE inhibitors. METHODS: Alzheimer's disease patients (121) were treated with cholinesterase inhibitors and the effect of treatment on cognition was measured using the Mini Mental State Examination (MMSE). Six polymorphisms in CHAT were analysed for association with change in MMSE score. RESULTS: After correction for multiple testing, we found one SNP, rs733722, in a promoter region of CHAT, is associated with response of AD patients to cholinesterase inhibitors (P = 0.03) and accounts for 6% of the variance in response to AChE inhibitors. CONCLUSION: Rs733722 represents a putative marker of response to AChE inhibitors in AD patients.

Aged↗
PubMed2004

Single nucleotide polymorphism genotyping by two colour melting curve analysis using the MGB Eclipse Probe System in challenging sequence environment.

Probe and primer design for single nucleotide polymorphism (SNP) detection can be very challenging for A-T DNA-rich targets, requiring long sequences with lower specificity and stability, while G-C-rich DNA targets present limited design options to lower GC-content sequences only. We have developed the MGB Eclipse Probe System, which is composed of the following elements: MGB Eclipse probes and primers, specially developed software for the design of probes and primers, a unique set of modified bases and a Microsoft Excel macro for automated genotyping, which ably solves, in large part, this challenge. Fluorogenic MGB Eclipse probes are modified oligonucleotides containing covalently attached duplex-stabilising dihydrocyclopyrroloindole tripeptide (DPI3), the MGB ligand (MGB is a trademark of Epoch Biosciences, Bothell, WA), which has the combined properties of allowing the use of short sequences and providing great mismatch discrimination. The MGB moiety prevents probe degradation during polymerase chain reaction (PCR), allowing the researcher to use real time data; alternatively, hybridisation can be accurately measured by a post-PCR two-colour melt curve analysis. Using MGB Eclipse probes and primers containing modified bases further enhances the analysis of difficult SNP targets. G- or C-rich sequences can be refractory to analysis due to Hoogsteen base pairing. Substitution of normal G with Epoch's modified G prevents Hoogsteen base pairing, allowing both superior PCR and probe-based analysis of GC-rich targets. The use of modified A and T bases allows better stabilisation by significantly increasing the Tm of the oligonucleotides. Modified A creates A-T base pairs that have a stability slightly lower than a G-C base pair, and modified T creates T-A base pairs that have a stability about 30 per cent higher than the unmodified base pair. Together, the modified bases permit the use of short probes, providing good mismatch discrimination and primers that allow PCR of refractory targets. The combination of MGB Eclipse probes and primers enriched with the MGB ligand and modified bases has allowed the analysis of refractory SNPs, where other methods have failed.

Base Sequence↗