Variants in the VCAM1 gene and risk for symptomatic stroke in sickle cell disease

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4303-4309 ◽  
Author(s):  
James G. Taylor VI ◽  
Delia C. Tang ◽  
Sharon A. Savage ◽  
Susan F. Leitman ◽  
Seth I. Heller ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Critical Role ◽  
Genome Project ◽  
Monogenic Disease ◽  
Candidate Snps ◽  
Healthy Population ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
A Cell ◽  
The Human Genome Project

Stroke is a major cause of morbidity and mortality in sickle cell (SS) disease. Genetic risk factors have been postulated to contribute to this clinical outcome. The human genome project has substantially increased the catalog of variations in genes, many of which could modify the risk for manifestations of disease outcome in a monogenic disease, namely SS. VCAM1 is a cell adhesion molecule postulated to play a critical role in the pathogenesis of SS disease. We identified a total of 33 single nucleotide polymorphisms (SNPs) by sequencing the entire coding region, 2134 bp upstream of the 5′ end of the published cDNA, 217 bp downstream of the 3′ end of the cDNA, and selected intronic regions of the VCAM1 locus. Allelic frequencies for selected SNPs were determined in a healthy population. We subsequently analyzed 4 nonsynonymous coding, 2 synonymous coding, and 4 common promoter SNPs in a genetic association study of clinically apparent stroke in SS disease conducted in a cohort derived from a single institution in Jamaica (51 symptomatic cases and 51 matched controls). Of the 10 candidate SNPs analyzed in this pilot study, the variant allele of the nonsynonymous SNP, VCAM1 G1238C, may be associated with protection from stroke (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.15-0.83, P = .04). Further study is required to confirm the importance of this variant inVCAM1 as a clinically useful modifier of outcome in SS disease.

scholarly journals In-silico analysis of non-synonymous-SNPs of STEAP2: To provoke the progression of prostate cancer

2016 ◽  
Vol 11 (1) ◽  
pp. 402-416 ◽  
Author(s):  
Muhammad Naveed ◽  
Sana Tehreem ◽  
Shamsa Mubeen ◽  
Fareeha Nadeem ◽  
Fatima Zafar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Three Dimensional ◽  
In Silico Analysis ◽  
Genome Project ◽  
Dimensional Structure ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Computational Tools ◽  
Epithelial Antigens ◽  
Novel Drug

AbstractAs a novel biomarker from the STEAP family, STEAP2 encodes six transmembrane epithelial antigens to prostate cancer. The overexpression of STEAP2 is predicted as the second most common cancer in the world that is responsible for male cancer-related deaths. Nonsynonymous SNPs are important group of SNPs which lead to alternations in encoded polypeptides. Changes in the amino acid sequence of gene products can lead to abnormal tissue function. The present study firstly sorted out those SNPs which exist in the coding region of STEAP2 and evaluated their impact through computational tools. Secondly, the three-dimensional structure of STEAP2 was formed through I-TASSER and validated by different software. Genomic data has been retrieved from the 1000 Genome project and Ensembl and subsequently analysed using computational tools. Out of 177 non-synonymous single nucleotide polymorphisms (nsSNPs) within the coding region, 42 mis-sense SNPs have been predicted as deleterious by all analyses. Our research shows a welldesigned computational methodology to inspect the prostate cancer associated nsSNPs. It can be concluded that these nsSNPs can play their role in the up-regulation of STEAP2 which further leads to progression of prostate cancer. It can benefit scientists in the handling of cancerassociated diseases related to STEAP2 through developing novel drug therapies.

scholarly journals A new discovery of genetic polymorphisms of important genes in WNT pathway (LPR5 and AXIN1) associated with osteoporosis susceptibility in Chinese Han population

2021 ◽  
Author(s):  
Yongsheng Cui ◽  
Xinglv Hu ◽  
Chen Zhang ◽  
Kunzheng Wang
Keyword(s):  
Protective Factor ◽  
Critical Role ◽  
Chinese Han Population ◽  
Candidate Snps ◽  
Classical Pathway ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Clinical Indicators ◽  
Han Population ◽  
Potential Association

Abstract Background: genetic factors play a critical role in the pathogenesis of osteoporosis. The imbalance of WNT/β-catenin will cause the occurrence of osteoporosis. LPR5 and AXIN1 play an important role in the classical Wnt/β-catenin signaling pathway. Our study was aimed to determine the association between 5 candidate single nucleotide polymorphisms (SNPs) of LPR5 or AXIN1 and osteoporosis susceptibility in Chinese Han population. Methods: the association analysis was conducted between 5 candidate SNPs and osteoporosis susceptibility among 1198 participants. Agena MassARRAY was used to genotype SNPs. The association between SNPs and osteoporosis susceptibility in different genetic models was analyzed by logistic regression analysis. Multi-factor dimension reduction (MDR) was used to analyze the interaction of SNP-SNP in the osteoporosis risk. The difference of clinical indicators under different genotypes was completed by one-way analysis of variance.Results: we found that LPR5 rs11228240, AXIN1 rs2301522 and rs9921222 were significantly associated with the osteoporosis susceptibility. The results of subgroup analysis showed that LPR5 rs11228240 (protective factor) and AXIN1 rs2301522 (risk factor) were significantly associated with the susceptibility of osteoporosis among participants who were age > 60 years, female or BMI≤24; AXIN1 rs9921222 significantly increased the risk of osteoporosis among participants with BMI≤24. The results of Haplotype analysis showed that Ars2301522Crs9921222 could increase the susceptibility of osteoporosis. We also found that LRP5 rs11228219, AXIN1 rs2301522 and rs9921222 showed a potential association with some clinical indicators of osteoporosis.Conclusion: the SNPs of LPR5 and AXIN1 which are important genes in WNT classical pathway, have a potential association with osteoporosis susceptibility in Chinese Han population.

RUNX1T1 rs34269950 is associated with obesity and metabolic syndrome

QJM ◽  
2020 ◽  
Author(s):  
Y Zhou ◽  
B D Hambly ◽  
D Simmons ◽  
C S McLachlan
Keyword(s):  
Metabolic Syndrome ◽  
Waist Circumference ◽  
Candidate Snps ◽  
Metabolic Abnormalities ◽  
Nucleotide Polymorphisms ◽  
Obesity Risk ◽  
Coding Region ◽  
Increased Risk ◽  
Related Transcription Factor ◽  
Transcription Factor 1

Summary Background Runt-related transcription factor 1 (RUNX1T1) isoforms are involved in adipogenesis. RUNX1T1 is mediated by the fat mass and obesity-associated (FTO). However, the extent to which RUNX1T1 single-nucleotide polymorphisms (SNPs) are associated with obesity risk or metabolic abnormalities in a community population basis is unknown. Methods Samples were obtained from the Australian Crossroads study bio-bank. SNPs located in the coding region and 3′untranslated regions of RUNX1T1 with minor allele frequency ≥0.05 were analysed using Taqman genotyping assays. Results Eight candidate SNPs were genotyped successfully in 1440 participants. Of these SNPs only rs34269950 located in the ‘RRACH’ motif, the most common N6-methyladenosine (m6A) methylation modification site (recognized by FTO), was significantly associated with obesity risk and metabolic abnormalities. Specifically, compared to AA genotype, rs34269950 del/del genotype was associated with a 1.47 [95% confidence interval (CI): 1.01–2.14, P = 0.042] fold higher rate of obesity risk. Additionally, the del/del genotype was associated with a 60% increased risk of metabolic syndrome (MetS) [odds ratio (OR) = 1.60, 95% CI: 1.10–2.32, P = 0.015], in comparison to the AA genotype. Finally, rs34269950 del/del increased the risk of a larger waist circumference (OR = 1.65, 95% CI: 1.15–2.36, P = 0.007), but not other components of MetS. Conclusion Our study demonstrates that RUNX1T1 rs34269950, located in a potential FTO recognition motif, is significantly associated with waist circumference. This provides novel evidence to suggest SNPs located in RRACH motif may be involved in RNA m6A modification and mechanistic pathways that influence abdominal obesity.

Present and future of genotype-based personalized nutrition

2014 ◽  
Vol 155 (20) ◽  
pp. 771-777
Author(s):  
Eszter Sarkadi Nagy ◽  
Éva Martos
Keyword(s):  
Human Genome Project ◽  
Scientific Evidence ◽  
Genome Project ◽  
Dietary Advice ◽  
Genetic Profile ◽  
Nucleotide Polymorphisms ◽  
Personalized Nutrition ◽  
Single Nucleotide ◽  
Multifactorial Diseases ◽  
The Human Genome Project

After the completion of the Human Genome Project, the era of providing personalized dietary advice based on an individual’s genetic profile seemed near. Since then more than a decade has passed and the pace of development has been slower than expected. Genotyping single nucleotide polymorphisms which may determine susceptibility to multifactorial diseases is cheaper and more accessible than it was ten years ago. However, few of them are supported by such solid scientific evidence which would justify their use for personalized dietary advice. The future of genotype-based personalized nutrition depends on whether a sufficient amount of gene–diet-disease interactions are identified and scientifically confirmed. Orv. Hetil., 2014, 155(20), 771–777.

DCC and RET pathway analysis to identify factors associated with advanced colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 457-457
Author(s):  
Stacey Shiovitz ◽  
Li Hsu ◽  
Conghui Qu ◽  
Tabitha A. Harrison ◽  
Sonja Berndt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Genome Project ◽  
P Value ◽  
Candidate Snps ◽  
Nucleotide Polymorphisms ◽  
Dependence Receptor

457 Background: DCC (deleted in colon cancer; 18q21.3) is frequently lost in colorectal cancers (CRC), but few mutations in DCC have been discovered, even in tumors with 18q loss of heterozygosity. DCC has been shown to be a dependence receptor, with differential signaling depending on the presence (proliferative) or absence (pro-apoptotic) of the netrin-1 ligand (NTN1). DCC-mutated CRC tend to present at advanced stage and have a poor prognosis. RET, another dependence receptor, is a possible tumor suppressor gene in CRC and associates with CRC progression. Given the apparent role of DCC and RET in CRC progression, we carried out a genetic association study to determine if specific genetic variants in these pathways associate with advanced vs. early CRC. Methods: Imputed HapMap genome-wide association study (GWAS) from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), a collection of 19 international case-control and cohort studies, was used to identify single nucleotide polymorphisms (SNPs) in DCC, NTN1, RET and interacting genes within 5kb upstream to 500mb downstream of each of the 54 genes. With the resultant 10,102 SNPs, we performed a stage-stratified analysis, comparing advanced (AJCC stage III-IV, n = 3500) to early CRC (I-II, n = 5300). An inverse-variance weighted fixed effect meta-analysis was performed with significance set at p=0.05/10102 SNPs=5x10-6 for multiple test correction. Results: Of the examined SNPs within DCC, the lowest p-value comparing advanced vs. early CRC was 3.6x10-3. SNPs in DOCK1 (dedicator of cytokinesis 1), which complexes with DCC and netrin-1, were associated with advanced CRC at p=1.11x10-3. SNPs in NTN1 and RET reached significance only at p = 1.73x10-2 and 1.53x10-2, respectively. No SNPs reached the pre-determined level of statistical significance. Conclusions: Our current analysis does not provide clear evidence for candidate SNPs associated with advanced CRC. Further approaches include expanding the analysis to include 1,000 Genome Project and ExomeChip data (~30,000 added SNPs), comparison of cases and controls, and evaluating candidate SNP-SNP interactions to better evaluate pathway pathogenesis. We plan to present an updated analysis at the symposium.

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