Abstract 662: Association Analysis of Raptor Gene Variants with Overweight and Hypertension in American Men of Japanese Ancestry

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Brian J Morris ◽  
Bruce A Carnes ◽  
Randi Chen ◽  
Timothy A Donlon ◽  
Qimei He ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Recursive Partitioning ◽  
Nucleotide Polymorphisms ◽  
Contingency Table Analysis ◽  
Hypertension Status ◽  
Predictive Capacity ◽  
Homogeneous Population ◽  
Table Analysis ◽  
Mtor Complex 1 ◽  
Japanese Ancestry

The mechanistic target of rapamycin (mTOR) pathway is pivotal for cell growth and has been implicated in aging, cardiovascular disease, obesity, diabetes and cancer. mTOR signaling is involved in cardiac leptin-mediated cardiac hypertrophy and fibrosis associated with obesity. mTOR is a key component of two multiprotein complexes, mTOR complex 1 and mTOR complex 2. The former is pro-growth and contains a unique protein, raptor. The present study tested for the first time whether genetic variation across the raptor gene ( RPTOR ) is associated with overweight/obesity, essential hypertension (EHT) and isolated systolic hypertension (ISH). We genotyped 61 common (allele frequency ≥ 0.1) tagging single nucleotide polymorphisms (SNPs) that captured most of the genetic variation across RPTOR in 374 subjects of normal lifespan and 439 subjects with a lifespan exceeding 95 years. Subjects were drawn from the Honolulu Heart Program, a homogeneous population of American men of Japanese ancestry, well characterized for phenotypes relevant to conditions of aging. Hypertension status was ascertained when subjects were 45–68 years old. Statistical evaluation was performed by contingency table analysis, logistic regression and recursive partitioning (RP), which is regarded as amongst the most powerful methods for statistical analysis of large complex sets of genetic information. After analysis of RPTOR genotypes by each statistical approach we found no significant association between genetic variation in RPTOR and either EHT or ISH. For EHT, RP revealed that even the most predictive SNPs ( rs4969322 and rs4890052 ) provided little contribution to correctly assigning individuals to EHT or NT ( P =0.22 by Z test). In the case of ISH, RP revealed that only one SNP ( rs2589118 ) made a noticeable contribution, and that this was no better than the contribution from the weakest laboratory/examination variable (overweight/obesity). In contrast, for overweight/obesity, the RP model revealed that RPTOR SNPs significantly enhanced the predictive capacity of the model ( P =0.008 by one-tailed Z test). In conclusion, genetic variation across RPTOR is associated with overweight/obesity, but not EHT or ISH in the populations of normal lifespan and of long-lived subjects studied.

scholarly journals Genomic Analyses of Globodera pallida, A Quarantine Agricultural Pathogen in Idaho

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 363
Author(s):  
Sulochana K. Wasala ◽  
Dana K. Howe ◽  
Louise-Marie Dandurand ◽  
Inga A. Zasada ◽  
Dee R. Denver
Keyword(s):  
Genetic Variation ◽  
Potato Production ◽  
Globodera Pallida ◽  
Fixation Index ◽  
Parasitic Nematodes ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Field Samples ◽  
Multiple Introduction

Globodera pallida is among the most significant plant-parasitic nematodes worldwide, causing major damage to potato production. Since it was discovered in Idaho in 2006, eradication efforts have aimed to contain and eradicate G. pallida through phytosanitary action and soil fumigation. In this study, we investigated genome-wide patterns of G. pallida genetic variation across Idaho fields to evaluate whether the infestation resulted from a single or multiple introduction(s) and to investigate potential evolutionary responses since the time of infestation. A total of 53 G. pallida samples (~1,042,000 individuals) were collected and analyzed, representing five different fields in Idaho, a greenhouse population, and a field in Scotland that was used for external comparison. According to genome-wide allele frequency and fixation index (Fst) analyses, most of the genetic variation was shared among the G. pallida populations in Idaho fields pre-fumigation, indicating that the infestation likely resulted from a single introduction. Temporal patterns of genome-wide polymorphisms involving (1) pre-fumigation field samples collected in 2007 and 2014 and (2) pre- and post-fumigation samples revealed nucleotide variants (SNPs, single-nucleotide polymorphisms) with significantly differentiated allele frequencies indicating genetic differentiation. This study provides insights into the genetic origins and adaptive potential of G. pallida invading new environments.

scholarly journals Genetic variation at the IGF1 locus shows association with post-stroke outcome and to circulating IGF1

2013 ◽  
Vol 169 (6) ◽  
pp. 759-765 ◽  
Author(s):  
N David Åberg ◽  
Sandra Olsson ◽  
Daniel Åberg ◽  
Katarina Jood ◽  
Tara M Stanne ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Ischemic Stroke ◽  
Stroke Severity ◽  
Stroke Outcome ◽  
Nucleotide Polymorphisms ◽  
Post Stroke ◽  
Index Stroke ◽  
Genetic Impact ◽  
Major Allele ◽  
Community Controls

ObjectiveIn humans, serum IGF1 (s-IGF1) is associated with outcome after ischemic stroke (IS). Therefore variation at the IGF1 locus could also associate with both IS and s-IGF1. We investigated whether genetic variation at the IGF1 locus is associated with i) s-IGF1, ii) IS occurrence, iii) IS severity, and iv) post-stroke outcome.Design/methodsPatients (n=844; 66% males, mean age 56 years) and community controls (n=668) were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Post-stroke outcome was evaluated with the modified Rankin Scale at 3 and 24 months after index stroke, and baseline stroke severity with the Scandinavian Stroke Scale. s-IGF1 was determined in patients and after random selection in 40 of the controls.ResultsEleven single nucleotide polymorphisms (SNPs) were selected in the IGF1 gene. In healthy controls the major allele of rs7136446 was associated with higher s-IGF1, whereas in patients no such association was found. No SNP was associated with IS, nor with stroke severity. After multivariate correction for presence of diabetes, smoking, and hypertension, the major allele of rs7136446 was associated with favorable functional outcome 24-months post-stroke (odds ratio 1.46; 95% CI 1.09–1.96).ConclusionVariation in rs7136446 of the IGF1 gene associates with post-stroke outcome in relatively young IS patients. Also, rs7136446 associates with s-IGF1 in controls but not in IS, which indicates that IS perturbs a normal genetic impact on s-IGF1 levels.

scholarly journals Biomarkers for Lifetime Caries-Free Status

2020 ◽  
Vol 11 (1) ◽  
pp. 23
Author(s):  
Ariana M. Kelly ◽  
Mariana Bezamat ◽  
Adriana Modesto ◽  
Alexandre R. Vieira
Keyword(s):  
Genetic Variation ◽  
Dental Caries ◽  
Protective Effect ◽  
Permanent Teeth ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Interacting Protein ◽  
Mandibular Molars ◽  
Matrix Metallopeptidase ◽  
Free Status

The purpose of this study was to address the hypothesis that extreme outcomes of dental caries, such as edentulism or prematurely losing permanent teeth are associated with genetic variation in enamel-formation genes. After scanning 6206 individuals, samples of 330 were selected for this study. Tested phenotypes included patients who were edentulous by age 30, patients with missing first molars by age 30, patients with missing second molars by age 30, and caries-free patients. Fourteen single nucleotide polymorphisms were genotyped by TaqMan chemistry. The analyses of each phenotype were performed using the software PLINK with an alpha of 0.05. Nominal associations were found between rs12640848 in enamelin (p = 0.05), rs1784418 in matrix metallopeptidase 20 (p = 0.02), and rs5997096 in the tuftelin interacting protein 11 and being caries-free at the age of 60. When combining patients that were missing both first mandibular molars and missing both second mandibular molars, no associations were found. Matrix metallopeptidase 20, and tuftelin interacting protein 11 also showed trends for association with being caries-free. Genetic variation in TFIP11, MMP20, and ENAM may have a protective effect increasing the chances of individuals preserving their teeth caries-free over a lifetime.

scholarly journals Single Nucleotide Polymorphism in SMAD7 and CHI3L1 and Colorectal Cancer Risk

2018 ◽  
Vol 2018 ◽  
pp. 1-23 ◽  
Author(s):  
Amal Ahmed Abd El-Fattah ◽  
Nermin Abdel Hamid Sadik ◽  
Olfat Gamil Shaker ◽  
Amal Mohamed Kamal
Keyword(s):  
Colorectal Cancer ◽  
Genetic Variation ◽  
Sequence Variation ◽  
Regulatory Protein ◽  
Nucleotide Polymorphisms ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
The Third ◽  
Common Cancer ◽  
Cancer Initiation

Colorectal cancer (CRC) is one of the leading cancers throughout the world. It represents the third most common cancer and the fourth in mortality. Most of CRC are sporadic, arise with no known high-penetrant genetic variation and with no previous family history. The etiology of sporadic CRC is considered to be multifactorial and arises from the interaction of genetic variants of low-penetrant genes and environmental risk factors. The most common well-studied genetic variation is single nucleotide polymorphisms (SNPs). SNP arises as a point mutation. If the frequency of the sequence variation reaches 1% or more in the population, it is referred to as polymorphism, but if it is lower than 1%, the allele is typically considered as a mutation. Lots of SNPs have been associated with CRC development and progression, for example, genes of TGF-β1 and CHI3L1 pathways. TGF-β1 is a pleiotropic cytokine with a dual role in cancer development and progression. TGF-β1 mediates its actions through canonical and noncanonical pathways. The most important negative regulatory protein for TGF-β1 activity is termed SMAD7. The production of TGF-βcan be controlled by another protein called YKL-40. YKL-40 is a glycoprotein with an important role in cancer initiation and metastasis. YKL-40 is encoded by the CHI3L1 gene. The aim of the present review is to give a brief introduction of CRC, SNP, and examples of some SNPs that have been documented to be associated with CRC. We also discuss two important signaling pathways TGF-β1 and CHI3L1 that influence the incidence and progression of CRC.

scholarly journals Assessing Summer Pond and Lake Inlet Use by Gray Treefrogs (Hyla versicolor/chrysoscelis complex) Using PVC Pipe Traps in Northwest Missouri

2020 ◽  
Vol 48 (2020) ◽  
pp. 17-21
Author(s):  
J. D. McGhee
Keyword(s):  
Sex Ratio ◽  
Hyla Versicolor ◽  
Monitoring Methods ◽  
Contingency Table Analysis ◽  
Detection Rates ◽  
Sampling Locations ◽  
Table Analysis ◽  
Pvc Pipe ◽  
Gray Treefrog

Abstract The widespread decline in amphibian populations highlights the need for establishing rigorous monitoring methods for long-term population studies. In an attempt to launch a long-term monitoring study for a Gray Treefrog complex (Hyla versicolor LeConte /chrysoscelis Cope, hereafter treefrog) population in northwest Missouri, I tested the use of PVC pipe traps in a system of ponds and inlets along a lakeside habitat for three years. For each pond (3) and inlet (2), I established an array of 16 pipes so as to compare differences in use between pipe location, ponds and inlets, and sex ratio between sites. Pipes were checked twice a week during the summer for the presence of treefrogs. Treefrog usage of pipes between ponds and inlets were compared using a contingency table analysis, while an ANOVA was used to assess differences in sex ratios between sites (α = 0.05). A single inlet was used by treefrogs more heavily than the other ponds or inlet (G = 13.61, df = 3, P = 0.0035), however, I found no differences in terms of pipe location within a pond or inlet. Mean sex ratio between water bodies varied but did not significantly differ. There appears to be little effect in terms of pipe placement within our 50 m buffer from the water's edge, but unique habitat effects at sampling locations may significantly affect detection rates or usage.

scholarly journals Genome-wide analyses reveal clustering in Cannabis cultivars: the ancient domestication trilogy of a panacea

2015 ◽  
Author(s):  
Philippe Henry
Keyword(s):  
Genetic Variation ◽  
Genetic Structure ◽  
Open Access ◽  
Nucleotide Polymorphisms ◽  
Data Set ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Access Data ◽  
Diagnostic Snps ◽  
Shed Light

In the present research, I used an open access data set (Medicinal Genomics) consisting of nearly 200'000 genome-wide single nucleotide polymorphisms (SNPs) typed in 28 cannabis accessions to shed light on the plant's underlying genetic structure. Genome-wide loadings were used to sequentially cull less informative markers. The process involved reducing the number of SNPs to 100K, 10K, 1K, 100 until I identified a set of 42 highly informative SNPs that I present here. The two first principal components, encompass over 3/4 of the genetic variation present in the dataset (PCA1 = 48.6%, PCA2= 26.3%). This set of diagnostic SNPs is then used to identify clusters into which cannabis accession segregate. I identified three clear and consistent clusters; reflective of the ancient domestication trilogy of the genus Cannabis.

Genetic Variation in the Syntaxin-Binding Protein STXBP5 in Type 1 von Willebrand Disease Patients

2018 ◽  
Vol 118 (08) ◽  
pp. 1382-1389 ◽  
Author(s):  
Christina Lind-Halldén ◽  
Eric Manderstedt ◽  
Daniel Carlberg ◽  
Stefan Lethagen ◽  
Christer Halldén
Keyword(s):  
Genetic Variation ◽  
Protein Function ◽  
Low Frequency ◽  
Von Willebrand Disease ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Swedish Population ◽  
Messenger Ribonucleic Acid ◽  
Von Willebrand

Abstractvon Willebrand factor (VWF) levels in healthy individuals and in patients with type 1 von Willebrand disease (VWD) are influenced by genetic variation in several genes, for example, VWF, ABO and STXBP5. Here, we comprehensively screen for STXBP5 variants and investigate their association with type 1 VWD in Swedish patients and controls. The coding region of the STXBP5 gene was re-sequenced in 107 type 1 VWD patients and the detected variants were genotyped in the type 1 VWD population and a Swedish control population (464 individuals). The functional effects of missense alleles were predicted in silico and the pattern of genetic variation in STXBP5 was analysed. Re-sequencing of 107 type 1 VWD patients identified three missense and three synonymous variants in the coding sequence of STXBP5. The low-frequency missense variants rs144099092 (0.005) and rs148830578 (0.029) were predicted to be damaging, but were not accumulated in patients. No other rare candidate mutations were detected. STXBP5 showed a high level of linkage disequilibrium and a low overall nucleotide diversity of π = 3.2 × 10−4 indicating intolerance to variants affecting protein function. Three previously type 1 VWD-associated single nucleotide polymorphisms were located on one haplotype that showed an increased frequency in patients versus controls. No differences in messenger ribonucleic acid abundance among haplotypes could be found using Genotype-Tissue Expression project data. In conclusion, a haplotype containing the STXBP5 Asn436Ser (rs1039084) mutation is associated with type 1 VWD and no rare STXBP5 mutations contribute to type 1 VWD in the Swedish population.

scholarly journals Risk Factors Associated With Femoral Ring Allograft Breakage in ALIF

2019 ◽  
Vol 11 (1) ◽  
pp. 57-62
Author(s):  
Travis Philipp ◽  
Stephanie S. Radoslovich ◽  
Jung U. Yoo
Keyword(s):  
Smoking Status ◽  
Retrospective Chart Review ◽  
Ordinary Least Squares ◽  
Continuous Variables ◽  
Least Squares Regression ◽  
Contingency Table Analysis ◽  
Femoral Ring ◽  
Table Analysis ◽  
Index Level ◽  
Comparison Patient

Study design: This is a retrospective chart review. Objectives: To identify the incidence of, and variables correlated with, femoral ring allograft (FRA) fracture following anterior lumbar interbody fusion (ALIF). Methods: All patients who underwent ALIF using FRAs at an academic institution over 10 years were included. Postoperative radiographs were reviewed by both the primary and senior authors; fracture and no-fracture groups were created for comparison. Patient and surgical characteristics were extracted from electronic medical records. Frequency data comparisons were performed using contingency table analysis; comparisons of means were analyzed for continuous variables. A multivariate linear regression model was developed using screw use, graft height <12 mm, index level, and weight as variables. Results: A total of 76 FRAs in 59 patients were identified, 13 (17%) of which fractured. Age, sex, smoking status, use of buttress screws, weight, index level, and presence of spondylolisthesis were not correlated with incidence of fracture ( P > .05). There was a significant correlation between the height of FRA and incidence of fracture; 2% (1/52) of grafts ≥12 mm and 50% (12/24) of grafts <12 mm fractured ( P < .0001). Using ordinary least-squares regression, this result was independent of patient weight, use of screws, and index level. Of 10 patients, 9 did not require revision surgery to achieve fusion. Conclusions: Graft height was the only variable correlated with incidence of FRA fracture. Graft height <12 mm is an independent risk factor for FRA fracture in patients undergoing ALIF, and their use should be avoided in ALIF procedures.

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