Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SNP analysis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources

Active microeletronic chip devices which utilize controlled electrophoretic fields for multiplex DNA hybridization and other genomic applications.

Microelectronic DNA chip devices that contain planar arrays of microelectrodes have been developed for multiplex DNA hybridization and a variety of genomic research and DNA diagnostic applications. These devices are able to produce almost any desired electric field configuration on their surface. This ability to produce well-defined electric fields allows charged molecules (DNA, RNA, proteins, enzymes, antibodies, nanobeads, and even micron scale semiconductor devices) to be electrophoretically transported to or from any microlocation on the planar surface of the device. Of key importance to the device function is the permeation layer which overcoats the microelectrodes. The permeation layer is generally a porous hydrogel material that allows water molecules and small ions (Na+, CI-, etc.) to freely contact the microelectrode surface, but impedes the transport of the larger analytes (oligonucleotides, DNA, RNA, proteins, etc.). The permeation layer prevents the destruction of DNA at the active microelectrode surface, ameliorates the adverse effects of electrolysis products on the sensitive hybridization reactions, and serves as a porous support structure for attaching DNA probes and other molecules to the array. In order to maintain rapid transport of DNA molecules, facilitate hybridization, and work within constrained current and voltage ranges, low conductance buffers and various electronic pulsing scenarios have also been developed. These active microelectronic array devices allow electrophoretic fields to be used to carry out accelerated DNA hybridization reactions and to improve selectivity for single nucleotide polymorphism (SNP), short tandem repeat (STR), and point mutation analysis.

Animals↗

Nitric oxide reduces nontransferrin-bound iron transport in HepG2 cells.

Nitric oxide (NO) donors S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside (SNP) modulate iron regulatory protein (IRP) activity and may, therefore, affect iron uptake through transferrin receptor expression. However, iron also enters the cell as nontransferrin-bound iron (NTBI), and the aim of this study was to evaluate the effects of NO donors on NTBI transport in HepG2 cells, a model of liver physiology. Incubation with SNP and SNAP led to a time- and concentration-dependent reduction in Fe3+ and Fe2+ uptake, thus indicating an effect on the transporter rather than on the reductase. In terms of Fe2+ uptake, no variations in the Michaelis-Menten constant (Km) and a reduction in maximum uptake (Vmax) (50, 33, and 16.6 fmol/microgram protein/min in control, SNP-, and SNAP-treated cells, respectively) were detected, which suggested a decrease in the number of putative NTBI transport protein(s). Gel shift assays showed that IRP activity was reduced by SNP and slightly increased by SNAP. Northern blot analysis of transferrin receptor messenger RNA (mRNA) levels showed variations similar to those observed for IRPs, but both NO donors increased L-ferritin mRNA levels and had no effect on the stimulator of Fe transport (SFT) mRNA. In conclusion, NO donors significantly reduce NTBI transport in HepG2 cells, an effect that seems to be IRP and SFT independent. Moreover, the reduction in NTBI uptake after NO treatment suggests that this form of iron may play a minor role in the increased hepatic iron stores observed in inflammation or that other liver cells are more involved in this pathological condition.

Apoptosis↗

Estimating the number of contributors to a DNA profile.

The broad topic of this paper is the evaluation of DNA evidence in criminal cases. More specifically, we deal with mixture evidence which refers to cases where there are, or could be, several contributors to a biological stain based on, e.g., blood or semen. The present paper addresses DNA mixtures based on single nucleotide polymorphism (SNP) markers, i.e., diallelic markers. Based on STR analysis, it is in most cases easy to identify the presence of a mixture since three or four bands will show up with a high probability for at least one locus. Obviously, this will not be the case for diallelic markers and interpreting mixtures will be a great challenge. We address this problem by first approaching the more general problem of estimating the number of contributors to a stain. In addition we discuss how the markers should be selected and how many are required.

Body Fluids↗

Polymorphisms in PNLIP, encoding pancreatic lipase, and associations with metabolic traits.

Pancreatic lipase (EC 3.1.1.3) is an exocrine secretion that hydrolyzes dietary triglycerides in the small intestine. We developed genomic amplification primers to sequence the 13 exons of PNLIP, which encodes pancreatic lipase, in order to screen for possible mutations in cell lines of four children with pancreatic lipase deficiency (OMIM 246600). We found no missense or nonsense mutations in these samples, but we found three silent single-nucleotide polymorphisms (SNPs), namely, 96A/C in exon 3, 486C/T in exon 6, and 1359C/T in exon 13. In 50 normolipidemic Caucasians, the PNLIP 96C and 486T alleles had frequencies of 0.083 and 0.150, respectively. The PNLIP 1359T allele was absent from Caucasian, Chinese, South Asian, and North American aboriginal samples, but had a frequency of 0.085 in an African sample, suggesting that it is a population-specific variant. In an association analysis of 185 African neonates, the PNLIP 1359C/T SNP genotype was significantly associated with concentrations of plasma lipoproteins. These associations were most likely due to linkage disequilibrium with another functional variant at or near PNLIP. Thus, we report three new SNPs for the PNLIP, which may serve as markers for association analyses and for pharmacogenetic studies of pancreatic lipase inhibitors.

Africa↗

MDA-MB-435 cells are derived from M14 melanoma cells--a loss for breast cancer, but a boon for melanoma research.

BACKGROUND: The tissue of origin of the cell line MDA-MB-435 has been a matter of debate since analysis of DNA microarray data led Ross et al. (2000, Nat Genet 24(3):227-235) to suggest they might be of melanocyte origin due to their similarity to melanoma cell lines. We have previously shown that MDA-MB-435 cells maintained in multiple laboratories are of common origin to those used by Ross et al. and concluded that MDA-MB-435 cells are not a representative model for breast cancer. We could not determine, however, whether the melanoma-like properties of the MDA-MB-435 cell line are the result of misclassification or due to transdifferention to a melanoma-like phenotype. METHODS: We used karyotype, comparative genomic hybridization (CGH), and microsatalite polymorphism analyses, combined with bioinformatics analysis of gene expression and single nucleotide polymorphism (SNP) data, to test the hypothesis that the MDA-MB-435 cell line is derived from the melanoma cell line M14. RESULTS: We show that the MDA-MB-435 and M14 cell lines are essentially identical with respect to cytogenetic characteristics as well as gene expression patterns and that the minor differences found can be explained by phenotypic and genotypic clonal drift. CONCLUSIONS: All currently available stocks of MDA-MB-435 cells are derived from the M14 melanoma cell line and can no longer be considered a model of breast cancer. These cells are still a valuable system for the study of cancer metastasis and the extensive literature using these cells since 1982 represent a valuable new resource for the melanoma research community.

Breast Neoplasms↗

Association of the M55L and Q192R paraoxonase gene polymorphisms with age-related macular degeneration.

PURPOSE: To investigate the reported association of the two single-nucleotide polymorphisms (SNPs) of the paraoxonase gene (PON1), Met-Leu 55 (M55L) and Gln-Arg 192 (Q192R), in individuals of Anglo-Celtic descent who have age-related macular degeneration (AMD). DESIGN: Case-control association study. METHODS: Sixty-two individuals with late (end-stage) AMD and 115 control subjects (without AMD) were included in this study. The M55L and Q192R SNPs were amplified by polymerase chain reaction and genotyped, and statistical analysis was undertaken. RESULTS: No association of either SNP was detected in persons of Anglo-Celtic descent who had AMD, although there was a significant difference in SNP allele frequency between Anglo-Celtic and Japanese individuals. CONCLUSION: The M55L and Q192R SNPs of the PON1 gene do not appear to be associated with late AMD in individuals of Anglo-Celtic descent.

Aged↗

Genotyping single nucleotide polymorphisms by MALDI mass spectrometry in clinical applications.

Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry has become one of the most powerful and widely applied technologies for SNP scoring and determination of allele frequencies in the post-genome sequencing era. Although different strategies for allele discrimination combined with MALDI were devised, in practice only primer extension methods are nowadays routinely used. This combination enables the rapid, quantitative, and direct detection of several genetic markers simultaneously in a broad variety of biological samples. In the field of molecular diagnostics, MALDI has been applied to the discovery of genetic markers, that are associated with a phenotype like a disease susceptibility or drug response, as well as an alternative means for diagnostic testing of a range of diseases for which the responsible mutations are already known. It is one of the first techniques with which whole genome scans based on single nucleotide polymorphisms were carried out. It is equally well suited for pathogen identification and the detection of emerging mutant strains as well as for the characterization of the genetic identity and quantitative trait loci mapping in farm animals. MALDI can also be used as a detection platform for a range of novel applications that are more demanding than standard SNP genotyping such as mutation/polymorphism discovery, molecular haplotyping, analysis of DNA methylation, and expression profiling. This review gives an introduction to the application of mass spectrometry for DNA analysis, and provides an overview of most studies using SNPs as genetic markers and MALDI mass spectrometric detection that are related to clinical applications and molecular diagnostics. Further, it aims to show specialized applications that might lead to diagnostic applications in the future. It does not speculate on whether this methodology will ever reach the diagnostic market.

Animals↗

"One Health"-based epidemiological investigation reveals the emergence of carbapenem-resistant Morganella spp. across diverse ecological niches.

OBJECTIVES: To investigate the prevalence, genomic relatedness, and resistance characteristics of carbapenemase-gene-positive Morganella spp. (CRM) across human, animal, fly, and aquatic sources. METHODS: A total of 163 Morganella isolates were collected from humans (n=124), animals (n=5), flies (n=21), aquatic environment (n=13) across 13 provinces or municipalities during 2018-2024. A subset of 71 representative isolates was subjected to antimicrobial susceptibility testing (AST), whole-genome sequencing and conjugation experiments. RESULTS: Among 163 isolates, 18 were carbapenemase-gene-positive: 15 carried blaNDM-1 alone, two carried blaKPC-2 alone, and one carried both genes. They were recovered from humans, flies, and hospital sewage. Five isolates carried blaPER-4; four carbapenemase-negative carriers were resistant to both ceftazidime/avibactam and aztreonam/avibactam. The aac(3)-IV gene was associated with high apramycin MICs and was most frequent in animal- and fly-derived isolates. Phylogenetic analysis showed diverse lineages, with limited low-SNP links between human and urban-river isolates. blaNDM-1 was transferred successfully from 11 of 16 donor isolates. CONCLUSION: CRM occur across multiple One Health niches. The findings highlight environmental and non-human reservoirs as potential contributors to their dissemination and identify blaPER-4 and aac(3)-IV as resistance-associated genes requiring further study.

Animal↗

Gene SNPs and mutations in clinical genetic testing: haplotype-based testing and analysis.

Haplotype-based analysis using high-density single nucleotide polymorphism (SNP) markers have gained increasing attention in evaluating candidate genes in various clinical situations. For example, haplotype information is useful for predicting the severity and prognosis of certain genetic disorders. The intragenic cis-interactions between the common polymorphisms and the pathogenic mutations of prion protein (PRNP) and cystic fibrosis transmembrane conductance regulator (CFTR) genes greatly influence the phenotypes and the disease penetrance of hereditary Creutzfeldt-Jakob disease and cystic fibrosis. Merits of haplotype study are more evident in the fine mapping of complex diseases and in identifying genetic variations that influence individual's response to drugs. Knowledge-based approaches and/or linkage analyses using SNP tagged haplotypes are effective tools in detecting genetic associations. For example, haplotype studies in the inflammatory bowel disease susceptibility loci revealed diverse cis and trans gene-gene interactions, which can affect the clinical outcomes. Although currently, we have very limited knowledge on haplotype-phenotypic characterizations of most genes, these examples demonstrate that increased understanding of the clinically relevant haplotypes will provide better results in the diagnosis and possibly in the treatment of both monogenic and polygenic diseases.

Amyloid↗

Human histamine N-methyltransferase pharmacogenetics: gene resequencing, promoter characterization, and functional studies of a common 5'-flanking region single nucleotide polymorphism (SNP).

Histamine N-methyltransferase (HNMT) catalyzes one of two major metabolic pathways for histamine. The levels of HNMT activity and immunoreactive protein in human tissues are regulated primarily by inheritance. Previous studies of HNMT identified two common single nucleotide polymorphisms (SNPs), including a functionally significant nonsynonymous coding SNP (cSNP), (C314T, Thr105Ile), but that polymorphism did not explain all of the phenotypic variation. In the present study, a genotype-to-phenotype strategy was used to search for additional genetic factors that might contribute to the regulation of human HNMT activity. Specifically, we began by resequencing the human HNMT gene using 90 ethnically anonymous DNA samples from the Coriell Cell Repository and identified a total of eight SNPs, including the two that had been reported previously. No new nonsynonymous cSNPs were observed, but three of the six novel SNPs were located in the 5'-flanking region (5'-FR) of the gene-including a third common polymorphism with a frequency of 0.367 (36.7%). That observation directed our attention to possible genetic effects on HNMT transcription. As a first step in testing that possibility, we created and studied a series of reporter gene constructs for the initial 1kb of the HNMT 5'-FR. The core promoter and possible regulatory regions were identified and verified by electrophoresis mobility shift assays. We then studied the possible functional implications of the new common HNMT 5'-FR SNP. However, on the basis of reporter gene studies, that SNP appeared to have little effect on transcription. Phenotype-genotype correlation analysis performed with 112 human kidney biopsy samples that had been phenotyped for their level of HNMT activity confirmed that the common 5'-FR SNP was not associated with the level of HNMT activity in vivo. In summary, this series of experiments resulted in the identification of several novel HNMT polymorphisms, identification of the HNMT core promoter, and a comprehensive functional genomic study of a common HNMT 5'-FR SNP. These results represent an additional step in the definition of molecular genetic mechanisms involved in the regulation of this important autacoid-metabolizing enzyme in humans.

5' Flanking Region↗

Association of a disintegrin and metalloprotease 33 (ADAM33) gene with asthma in ethnically diverse populations.

BACKGROUND: Asthma is a complex genetic disease characterized by reversible intermittent airway obstruction and respiratory symptoms primarily caused by acute and chronic bronchial inflammation. Recently, a gene potentially involved in airway remodeling, a disintegrin and metalloprotease 33 (ADAM33), was implicated in asthma susceptibility. OBJECTIVE: We sought to determine whether polymorphisms in ADAM33 are associated with asthma or closely related phenotypes in 4 different asthma populations. METHODS: Eight single nucleotide polymorphisms (SNPs) were evaluated in the 3' portion of ADAM33 in 4 unique asthma populations (African American, US white, US Hispanic, and Dutch white). These SNPs were previously reported to be associated with asthma in white populations from the United States and United Kingdom. RESULTS: Significant associations were observed with at least one SNP and asthma in each population (P =.0009-.04). Related phenotypes that included total serum IgE levels and skin test responsiveness were also associated (P =.003-.05). However, no single SNP was associated across all populations. Additionally, haplotype analysis revealed that no single haplotype accounted for asthma susceptibility risk, although potential risk haplotypes existed within some of the populations. CONCLUSION: Replication of the original ADAM33 findings in these 4 additional asthma populations suggests that this gene (and perhaps others that interact with it) is important in the development and pathogenesis of asthma.

ADAM Proteins↗

Application of SNPs for assessing biodiversity and phylogeny among yeast strains.

We examined the efficacy of single-nucleotide polymorphism (SNP) markers for the assessment of the phylogeny and biodiversity of Saccharomyces strains. Each of 32 Saccharomyces cerevisiae strains was genotyped at 30 SNP loci discovered by sequence alignment of the S. cerevisiae laboratory strain SK1 to the database sequence of strain S288c. In total, 10 SNPs were selected from each of the following three categories: promoter regions, nonsynonymous and synonymous sites (in open reading frames). The strains in this study included 11 haploid laboratory strains used for genetic studies and 21 diploids. Three non-cerevisiae species of Saccharomyces (sensu stricto) were used as an out-group. A Bayesian clustering-algorithm, Structure, effectively identified four different strain groups: laboratory, wine, other diploids and the non-cerevisiae species. Analysing haploid and diploid strains together caused problems for phylogeny reconstruction, but not for the clustering produced by Structure. The ascertainment bias introduced by the SNP discovery method caused difficulty in the phylogenetic analysis; alternative options are proposed. A smaller data set, comprising only the nine most polymorphic loci, was sufficient to obtain most features of the results.

Biodiversity↗

Association study of an SNP combination pattern in the dopaminergic pathway in paranoid schizophrenia: a novel strategy for complex disorders.

Schizophrenia is a common mental disorder with a complex pattern of inheritance. Despite a large number of studies in the past decades, its molecular etiology remains unknown. In this study, we proposed a 'system-thinking' strategy in seeking the combined effect of susceptibility genes for a complex disorder by using paranoid schizophrenia as an example. We genotyped 85 reported single-nucleotide polymorphisms (SNPs) present in 23 genes for the dopamine (DA) metabolism pathway among 83 paranoid schizophrenics and 108 normal controls with detailed clinical and genetic information. We developed two novel multilocus approaches-the potential effective SNP combination pattern and potential effective dynamic effects analysis, by which three susceptibility genotype combinations were found to be associated with schizophrenia. These results were also validated in a family-based cohort consisting of 95 family trios of paranoid schizophrenia. The present findings suggest that the COMT and ALDH3 combination may be the most common type involved in predisposing to schizophrenia. Since the combination blocks the whole pathways for the breakdown of DA and noradrenaline, it is very likely to play a central role in developing paranoid schizophrenia.

Adolescent↗

Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood with substantial heritability. Pharmacological and molecular genetic studies as well as characterization of animal models have implicated serotonergic dysfunction in the pathophysiology of ADHD. Here, we investigated the effect of polymorphic variants in the gene of the tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme of serotonin (5-HT) synthesis in the brain, in children and adolescents with ADHD. We analyzed three single nucleotide polymorphisms (SNPs) in and downstream of the transcriptional control region of the TPH2 gene in 103 families with 225 affected children. Allelic association in families with more than one affected child was assessed using the pedigree disequilibrium test. Preferential transmissions were detected for the two SNPs in TPH2's regulatory region (rs4570625, P=0.049; rs11178997, P=0.034), but not for the third SNP in intron 2 (rs4565946, P=0.3517). Haplotype analysis revealed a strong trend of association between the regulatory region SNPs (rs4570625, rs11178997) and ADHD (P=0.064). Our results link potentially functional TPH2 variations to the pathophysiology of ADHD, and further support the relevance of 5-HT in disorders related to altered motor activity and cognitive processes.

Adolescent↗

Nitric oxide induces heme oxygenase-1 gene expression in mesangial cells.

BACKGROUND: Nitric oxide (NO) release as a result of activation of inducible NO synthase (iNOS) can be sustained and reach cytotoxic concentrations. It is unknown whether cells possess intrinsic systems to attenuate NO-mediated cytotoxicity. One potential system is the heme oxygenase-1 (HO-1) enzyme because it catabolizes heme and therefore may limit synthesis or availability of iNOS. These studies were undertaken to explore whether NO derived from NO donors or from activation of iNOS induces HO-1 in mesangial cells. METHODS: The expression of the HO-1 gene was evaluated at the mRNA (Northern blot analysis) and protein (Western blot analysis) levels in mesangial cells treated with two NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetyl-DL-penicillamine (SNAP), or was stimulated by the combination of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) to induce iNOS in the presence and absence of NOS inhibitor NG-Monomethyl-L-arginine (L-NMMA). RESULTS: HO-1 was constitutively expressed in mesangial cells. Both SNP and SNAP induced HO-1 mRNA in a dose-dependent manner. The increase in mRNA was associated with an increase in HO-1 protein in SNP-treated cells. The combination of the LPS/IFN-gamma mixture induced iNOS expression and NO production in murine mesangial cells, as assessed by Western blot analysis and measurement of nitrite levels. HO-1 expression was also increased in response to LPS/IFN-gamma. L-NMMA dose dependently attenuated HO-1 mRNA and protein levels. In contrast, iNOS expression was dose dependently enhanced. CONCLUSIONS: Our studies demonstrate that both exogenously or iNOS-derived NO enhance HO-1 expression in mesangial cells and point to regulatory interactions between the iNOS and HO pathways. HO-1 activation may defend against NO-mediated toxicity.

Animals↗

Genomewide distribution of high-frequency, completely mismatching SNP haplotype pairs observed to be common across human populations.

Knowledge of human haplotype structure has important implications for strategies of disease-gene mapping and for understanding human evolutionary history. Many attributes of SNPs and haplotypes appear to exhibit highly nonrandom behavior, suggesting past operation of selection or other nonneutral forces. We report the exceptional abundance of a particular haplotype pattern in which two high-frequency haplotypes have different alleles at every SNP site (hence the name "yin yang haplotypes"). Analysis of common haplotypes in 62 random genomic loci and 85 gene coding regions in humans shows that the proportion of the genome spanned by yin yang haplotypes is 75%-85%. Population data of 28 genomic loci in Drosophila melanogaster reveal a similar pattern. The high recurrence (>/=85%) of these haplotype patterns in four distinct human populations suggests that the yin yang haplotypes are likely to predate the African diaspora. The pattern initially appeared to suggest deep population splitting or maintenance of ancient lineages by selection; however, coalescent simulation reveals that the yin yang phenomenon can be explained by strictly neutral evolution in a well-mixed population.

Algorithms↗

Harnessing Polygenic Risk Scores to Refine Venous Thromboembolism Risk Stratification.

BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity in patients of all ages. Despite growing interest in polygenic risk scores (PRS) for VTE, their utility remains understudied. Our objective was to evaluate the independent impact of a PRS on VTE susceptibility in adults and children. METHODS: We completed a retrospective, case-control study of two separate cohorts with evaluation of three VTE PRS models, with the primary analysis focused on a 293 single nucleotide polymorphism (SNP) PRS. The adult cohort included 597 VTE cases and 31&#x2009;998 controls, and the pediatric cohort included 109 cases and 448 controls, both obtained from a de-identified databank with linked genetic data. Separate adult and pediatric multivariable logistic regressions were performed to measure the association of risk factors with VTE. RESULTS: Higher PRS in adults was significantly associated with increased odds of VTE, with each 1-standard deviation increase in PRS conferring an adjusted odds ratio of 1.25 (OR&#x2009;=&#x2009;1.25, 95% CI 1.15-1.36, p&#x2009;<&#x2009;0.001). Leading risk factors for adults were cancer (OR&#x2009;=&#x2009;2.43, 95% CI: 2.04-2.89, p&#x2009;<&#x2009;0.001) and recent surgery (OR&#x2009;=&#x2009;2.16, 95% CI: 1.83-2.54, p&#x2009;<&#x2009;0.001). The standardized PRS also exhibited increased risk for VTE in children (OR&#x2009;=&#x2009;1.38, 95% CI 1.10-1.74, p&#x2009;=&#x2009;0.003). Central venous catheterization (OR&#x2009;=&#x2009;5.65, 95% CI 3.40-9.50, p&#x2009;<&#x2009;0.001) was the foremost risk factor for pediatric VTE. CONCLUSION: VTE in adults and children is multifactorial, with clinical and genome-wide risk factors contributing. PRS may serve as a valuable adjunct to clinical risk factors for VTE risk stratification.

Humans↗

Haplotypes in the tumour necrosis factor region and myeloma.

This study described the haplotypic structure across a region of chromosome 6 including the tumour necrosis factor (TNF) gene, and investigated its influence on the aetiology of myeloma. A total of 181 myeloma cases from the Medical Research Council Myeloma VII trial and 233 controls from the Leukaemia Research Fund Case Control Study of Adult Acute Leukaemia were included in the analysis. Genotyping by induced heteroduplex generator analysis was carried out for single nucleotide polymorphisms (SNP) located at positions -1031, -863, -857, -308 and -238 of the 5' promoter region of TNF-alpha gene, and 252 in the LT-alpha gene; and five microsatellites, TNFa, b, c, d and e. Haplotypes were inferred statistically using the phase algorithm. A limited diversity of haplotypes was observed, with the majority of variation described by 12 frequent haplotypes. Detailed characterization of the haplotype did not provide greater determination of disease risk beyond that described by the TNF-alpha-308 SNP. Some evidence was provided for a decreased risk of myeloma associated with the TNF-alpha-308 variant allele A, odds ratio, 0.57; 95% confidence interval, 0.38-0.86. The results of this study did not support our starting hypothesis; that high producer haplotypes at the TNF locus are associated with an increased risk of developing myeloma.

Adult↗