scholarly journals Evaluation of Age-Gene Correlation and the Association with Hypertriglyceridemia Using Adiponectin Receptor Single Nucleotide Polymorphism: A Potential Genetic Screening to Lower Risk of Vascular Disease in Young Asian Males

2017 ◽  
Vol 7 (2) ◽  
pp. 61
Author(s):  
William C. W. Huang ◽  
Yi-MeiJoy Lin ◽  
Ching Che J. Chiu ◽  
Chia-Huei Chiu ◽  
Fu-Sheng Chang

Purpose: This study was to investigate whether there is an age dependent effect on the association between ADIPPOR1 SNP and hypertriglyceridemia for each gender.Materials and Methods: 116 individuals aged 20 and above who claimed to be healthy were enrolled and grouped into male and female populations. Blood samples were taken to determine hypertriglyceridemia and genomic variants. Sample t-tests were performed for basic comparison. To ascertain the contribution of genetic variants and age to lipid metabolism, a multivariate logistic regression analysis was conducted to identify the correlates for hypertriglyceridemia adjusting for life styles.Results: For males, individuals with hypertriglyceridemia tended to be younger (p-value=0.02), less stressed (0.05), and have a higher proportion of ADIPOR1 minor allele carriers (0.03). However, no significant differences were found in age, stress, diet, and genetic variances in females. In regression analysis, males showed age-gene correlation with 1.5 times higher detection of hypertriglyceridemia risk when both factors were considered. In contrast, females showed no correlation between age-gene. In addition, age was positively associated with hypertriglyceridemia in females while males showed an inverse association.Conclusion: Our findings presented data that suggests age may be a contributing factor to the association between ADIPOR1 and hypertriglyceridemia in males while age showed a significant inverse association with hypertriglyceridemia. Thus, age-gene correlation may be implied during primary practice to encourage lifestyle adjustments by screening for ADIPOR1 SNP minor allele carriers to prevent cerebrovascular disease in males.

2021 ◽  
pp. 175342592110299
Author(s):  
Alexander Varzari ◽  
Igor V. Deyneko ◽  
Elena Tudor ◽  
Harald Grallert ◽  
Thomas Illig

Polymorphisms in genes that control immune function and regulation may influence susceptibility to pulmonary tuberculosis (TB). In this study, 14 polymorphisms in 12 key genes involved in the immune response ( VDR, MR1, TLR1, TLR2, TLR10, SLC11A1, IL1B, IL10, IFNG, TNF, IRAK1, and FOXP3) were tested for their association with pulmonary TB in 271 patients with TB and 251 community-matched controls from the Republic of Moldova. In addition, gene–gene interactions involved in TB susceptibility were analyzed for a total of 43 genetic loci. Single nucleotide polymorphism (SNP) analysis revealed a nominal association between TNF rs1800629 and pulmonary TB (Fisher exact test P = 0.01843). In the pairwise interaction analysis, the combination of the genotypes TLR6 rs5743810 GA and TLR10 rs11096957 GT was significantly associated with an increased genetic risk of pulmonary TB (OR = 2.48, 95% CI = 1.62–3.85; Fisher exact test P value = 1.5 × 10−5, significant after Bonferroni correction). In conclusion, the TLR6 rs5743810 and TLR10 rs11096957 two-locus interaction confers a significantly higher risk for pulmonary TB; due to its high frequency in the population, this SNP combination may serve as a novel biomarker for predicting TB susceptibility.


Plants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 425
Author(s):  
Chinyere F. Anagbogu ◽  
Christopher O. Ilori ◽  
Ranjana Bhattacharjee ◽  
Olufemi O. Olaniyi ◽  
Diane M. Beckles

The flavor and health benefits of coffee (Coffea spp.) are derived from the metabolites that accumulate in the mature bean. However, the chemical profiles of many C. canephora genotypes remain unknown, even as the production of these coffee types increases globally. Therefore, we used Gas Chromatography-Mass Spectrophotometry to determine the chemical composition of C. canephora genotypes in Nigeria—those conserved in germplasm repositories and those cultivated by farmers. GC-MS revealed 340 metabolites in the ripe beans, with 66 metabolites differing (p-value < 0.05) across the represented group. Univariate and multivariate approaches showed that the ‘Niaouli’ genotypes could be clearly distinguished from ‘Kouillou’ and ‘Java’ genotypes, while there was almost no distinction between ‘Kouillou’ and ‘Java,’. Varietal genotyping based on bean metabolite profiling was synchronous with that based on genome-wide Single Nucleotide Polymorphism analysis. Across genotypes, the sucrose-to-caffeine ratio was low, a characteristic indicative of low cup quality. The sucrose-to-caffeine ratio was also highly correlated, indicative of common mechanisms regulating the accumulation of these compounds. Nevertheless, this strong correlative link was broken within the ‘Niaouli’ group, as caffeine and sucrose content were highly variable among these genotypes. These ‘Niaouli’ genotypes could therefore serve as useful germplasm for starting a Nigerian C. canephora quality improvement breeding program.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 86-86
Author(s):  
Nicole Soranzo ◽  
Marloes R. Tijssen ◽  
Augusto Rendon ◽  
Christine Meisinger ◽  
Chris I. Jones ◽  
...  

Abstract The variation in blood cell indices between individuals is to a large extent genetically controlled. In the normal population mean platelet volume (MPV) is inversely correlated with platelet count. We undertook a genome-wide association analysis of MPV on 2.5 million imputed genotypes in 1,475 individuals from the UK Blood Services Common Controls, followed by replication in an additional 7,098 samples from four independent collections. We identified a novel locus on chromosome 7q22.3, in a region frequently deleted in myeloid malignancies, where the lead single nucleotide polymorphism (SNP) had a highly significant association with MPV (average G allele effect size 0.15 log fl, 95% CI 0.0118–0.0174, P-value = 9.5×10−24) and an opposite effect on platelet counts (G allele effect −4.51 109/l, 95% CI −6.112 - −2.900, P-value = 1.46×10−7), but the SNP did not exert an effect on red cell indices. The lead SNP with a minor allele frequency of 0.46 is intergenic between the hypothetical gene FLJ36031 and the PIK3CG gene. There are 6 genes in the 1-Mb window centred around the lead SNP and all but HBP1 are transcribed in megakaryocytes (MKs) and to a variable degree in the other seven blood cell lineages. The formation and regulation of volume of platelets is critically dependent on the interaction of MK-expressed integrins with extracellular matrix proteins like fibrinogen and collagen. This prompted us to analyze, in our platelet function cohort of 500 healthy individuals, the association between the lead SNP and binding of both fibrinogen and annexin V to platelets following activation with the collagen mimetic CRP-XL, both associations were significant, with P-values of 0.05 and 0.003, respectively. In summary, we describe a common SNP associated with differences in volume, count and function of platelets from healthy individuals. Intriguingly, our results indicate that the same 7q22.3 region which is frequently deleted in myeloid malignancies harbours important regulatory elements of several platelet phenotypic traits.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4257-4257
Author(s):  
Gordon D. McLaren ◽  
Catherine A. McCarty ◽  
Marylyn Ritchie ◽  
Stephen Turner ◽  
Victor R. Gordeuk ◽  
...  

Abstract Abstract 4257 Iron in the plasma is bound to transferrin. The total iron binding capacity (TIBC) represents the maximum amount of iron that can be bound and is directly related to transferrin concentration. TIBC and serum transferrin concentration are increased in iron deficiency and decreased in iron overload. Recently, an association was reported between single nucleotide polymorphisms (SNPs) in the transferrin gene, TF, on chromosome 3q22.1, and serum transferrin levels (Benyamin et al. Am J Hum Genet. 2009;84:60-65). In the current study, we investigated whether the association between SNP rs3811647 in TF and transferrin levels (assessed by measurement of TIBC) is attributable to an effect on regulation of body iron status. The Personalized Medicine Research Project (PMRP) is the largest population-based biobank in the US containing genetic, phenotypic and environmental information on approximately 20,000 people. PMRP is part of the NHGRI-funded eMERGE (www.gwas.net) network. Previously, genotyping was performed on selected PMRP samples with the Illumina Human660W-Quad BeadChip platform. Eligible participants in the current study were 491 white men age ≥ 25 y and 747 white women ≥ 50 y with serum ferritin (SF) values collected between 1985 and 2010. Exclusion criteria included a diagnosis of celiac disease and previous phlebotomy treatment for hemochromatosis. Using TIBC as a marker of serum transferrin for eligible participants having multiple measurements, mean TIBC and median serum ferritin were considered in analyses. Subsets of participants included cases of iron deficiency with multiple measurements of SF ≤ 12 μg/L and iron-replete controls (all measurements of SF > 100 μg/L in men, all SF > 50 μg/L in women). Regression analysis was used to examine the association between outcomes (case-control status, natural log of serum ferritin, TIBC) and each of 54 SNPs, adjusted for gender. These SNPS included three in iron genes (rs3811647 in TF, rs1800562 in HFE, and rs2302591 in FLVCR2) and were selected for analysis on the basis of a GWAS of iron-related measures conducted in a separate study of iron deficient cases and iron-replete controls identified in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Statistical significance was defined as a SNP showing a p-value for association less than 0.001; the threshold is based on a nominal alpha of 0.05 with Bonferroni multiple test correction for the total number of SNPs analyzed. Genotypes were coded as 0, 1, or 2, indicating the number of copies of the less frequent of the two alleles in the genotype. Values for mean TIBC were analyzed for 1175 individuals (726 women, 449 men); median SF was analyzed for 1143 participants (693 women, 450 men). In the subset analyses, there were 258 cases with iron deficiency and 505 controls. The strongest statistical evidence for association with TIBC was found for SNP rs3811647 in the TF gene (observed p-value = 6.05 × 10-6, adjusted for gender). The minor allele frequency for SNP rs3811647 was 0.34. The regression slope parameter was 14.5, indicating that increasing copies of the minor allele were associated with increasing levels of TIBC. In contrast, there was no significant association with SF (observed p=0.22) or case vs. control status (odds ratio 1.26, observed p=0.21), adjusted for gender. For the C282Y mutation in the HFE gene, increasing copies of the minor allele were associated with decreasing levels of TIBC (observed p-value = 0.002, adjusted for gender). The fact that SNP rs3811647 in the TF gene was associated with TIBC levels but showed no significant association with either serum ferritin or the presence of iron deficiency does not support a role for the SNP in regulation of body iron status. Thus, the SNP may affect TIBC independently of iron status. Elevation of transferrin levels could help withhold iron from microorganisms, conferring protection from infection. Use of TIBC as an index of iron deficiency may be confounded by the existence in the population of the minor allele in the rs3811647 genotype, resulting in elevation of TIBC without a corresponding decrease in body storage iron. Disclosures: No relevant conflicts of interest to declare.


2010 ◽  
Vol 28 (4) ◽  
pp. 578-585 ◽  
Author(s):  
Frederik Damm ◽  
Michael Heuser ◽  
Michael Morgan ◽  
Haiyang Yun ◽  
Anika Großhennig ◽  
...  

Purpose We assessed the prognostic impact of a known single nucleotide polymorphism (SNP) located in the mutational hotspot of WT1 in patients with cytogenetically normal acute myeloid leukemia (CN-AML) in the context of other prognostic markers. Patients and Methods WT1 exons 7 and 9 from 249 CN-AML patients from multicenter treatment trials AML-SHG Hannover 0199 (Clinical Trials Identifier NCT00209833) and 0295, and 50 healthy volunteers were analyzed by direct sequencing. NPM1, FLT3, CEBPA, and MLL were assessed for mutations and WT1 expression was quantified. Results The minor allele of SNP rs16754 (WT1AG/GG) was found in 25.7% of CN-AML patients' blasts and germline DNA and in 36% of healthy volunteers. Patient characteristics, frequencies of mutations, or WT1 expression levels were similarly distributed between patients homozygous for the major allele compared with patients heterozygous or homozygous for the minor allele. SNP rs16754 status was an independent predictor of relapse-free survival (RFS; hazard ratio [HR], 0.49; 95% CI, 0.3 to 0.81; P = .005) and overall survival (OS; HR, 0.44; 95% CI, 0.27 to 0.74; P = .002) in multivariate analysis. The favorable effect of SNP rs16754 was stronger in NPM1/FLT3-ITD (internal tandem duplication of the FLT3 gene) high-risk patients compared with NPM1/FLT3-ITD low-risk patients. Favorable prognosis could not be identified by any other known low-risk marker in half the patients with at least one minor allele (13% of all patients). No difference for complete remission rate, RFS, or OS was found between patients with or without acquired WT1 mutations. Conclusion WT1 SNP rs16754 may be a novel independent favorable-risk marker in CN-AML patients that might improve risk and treatment stratification.


2021 ◽  
Vol 2 (3) ◽  
pp. 66-71
Author(s):  
Salman Imtiaz ◽  
Ashar Alam ◽  
Faiza Saeed ◽  
Beena Salman ◽  
Shoukat Memon ◽  
...  

Background: Corona virus disease (Covid -19) is the most contagious form of the disease of present time. Therefore, the risk factors which proliferate the spread and hinders the better outcome should be identified. There is gross difference in the spread and outcome of covid 19 in different region of the world. There is need to identify these factors in different communities of the globe. Material and method: This is a retrospective observational cohort study of Covid -19 patients admitted during the study period. Institutional and ethical review board permission was taken prior to the study. Univariate and multivariate binary logistic regression was run and odds ratio with 95% confidence intervals were obtained. P value of ≤ 0.05 was considered significant. Outcome variables were recovery and death. Results: There were 840 patients admitted between the study duration, while 704 (83.8%) were included in our study. There were 491(69.7%) males and 213(30.3%) females. The mean age of the population was 54.6±15.5 years. All continuous variables were categorized according to binary outcome (recovered and death) of patients. In Logistic regression analysis we found that patients in age group of 51-65 years died 2.5 time more than patients of age ≤ 50 years. Similarly, the patients within age group of > 65 died 4.5 times higher than ≤ 50 years of age (p<0.001). Male patients died 1.5 times more than females. Among all comorbid conditions HTN had significant effect on death, they died 1.5 times more than normotensive patients. In multivariate logistic regression analysis, the age groups had same significant effect on death when adjusted with other parameters, while effect of gender vanished. Similarly, the effect of HTN was also abolished when other factors were included in analysis. Conclusion: We concluded that there is an urgent need of reevaluation of the traditional risk factors associated with viral epidemic and understanding the changing paradigm of epidemiology emerging out from this epidemic in both developed and developing counties. There is need of more data from developing world to elucidate the risk factors.


Genetika ◽  
2016 ◽  
Vol 48 (3) ◽  
pp. 819-826 ◽  
Author(s):  
Sajjad Ghorghanlu ◽  
Mohammad Asgharzadeh ◽  
Hossein Samadi-Kafil ◽  
Fatemeh Khaki-Khatibi ◽  
Jalil Rashedi ◽  
...  

Single nucleotide polymorphisms (SNPs) in cytokine genes may alter the level and function of secreted cytokine; therefore, SNPs can influence the immune response. The aim of the present study was to determine the association of TNF-? -308G/A single nucleotide polymorphism in tuberculosis patients in the Azeri population of Iran. The TNF-308G/A single nucleotide polymorphism in the promoter region was genotyped by using the allele-specific PCR method in 200 healthy controls and 124 tuberculosis patients. The distribution of allele frequencies for TNF-? -308G/A polymorphism between control and tuberculosis patient groups was not significant (P-value = 0.058, OR = 1.5). Furthermore, no statistically significant association was found between TNF-? -308G/A genotype and resistance/susceptibility to TB (P-value = 0.102). Our results suggest that TNF-? -308G/A polymorphism has no measurable effect on the development of tuberculosis in Azeri population of Iran.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 661-661
Author(s):  
Animesh Pardanani ◽  
Brooke Fridley ◽  
Terra Lasho ◽  
Sara Achenbach ◽  
D. Gary Gilliland ◽  
...  

Abstract Background: Constitutive activation of the JAK-STAT signaling pathway through acquisition of the JAK2V617F mutation plays a key role in the pathogenesis of related myeloproliferative disorders (MPD) including polycythemia vera (PV), agnogenic myeloid metaplasia (AMM), and essential thrombocythemia (ET). Hypothesis: Genetic variation in JAK2 and/or the cytokine receptor genes for erythropoietin (EPOR), thrombopoietin (MPL), and granulocyte colony stimulating factor (GCSFR), influences the expression of a specific disease phenotype (PV, AMM, or ET). Methods: We studied 179 Caucasian MPD patients (PV=84, AMM=58, ET=37) for genetic variation in 4 candidate genes (i.e. JAK2, EPOR, MPL, GCSFR) through single nucleotide polymorphism (SNP) and haplotype analyses. A total of 32 LD (linkage disequilibrium) tag-SNPs with a minimum allele frequency of at least 5% were selected from the HapMap CEU database (JAK2=13, EPOR=4, MPL=5, GCSFR=10). Genotyping was performed using archived DNA from enriched neutrophils. Results: Seventy six (94%), 26 (45%), and 14 (38%) patients with PV, AMM, and ET, respectively, carried the JAK2V617F mutation. Significant differences in allele frequencies was observed at 6 SNP loci (rs10758669, rs3808850, rs7849191, rs7046736, rs10815148, and rs12342421, p-values &lt; 0.0005), all within the JAK2 gene, in comparing our overall study population with the founder Caucasian population in the HapMap database. In the additive genotype-phenotype association analysis adjusted for gender and age at diagnosis, 3 SNP loci in JAK2 (rs7046736, rs10815148, and rs12342421) were found to be significantly, but reciprocally associated with PV (p-values &lt; 0.00006, odds ratio=0.37, 2.82, and 2.39, respectively) and ET (p-values &lt; 0.002, odds ratio=2.50, 0.36, and 0.41, respectively), but not AMM, in terms of the minor allele being ’protective’. These three SNPs were all in high LD, with the ’r2’ measures of LD between 0.59 and 0.71. Furthermore, 2 additional JAK2 SNP loci (rs10758669, p-value = 0.0024 and rs10974947, p-value = 0.0046) were significantly associated with PV (odds ratio=1.88 and 0.47, respectively), but not ET or AMM. Similarly, presence of the minor allele at a single SNP locus in EPOR (rs318699, p-value = 0.0012) was significantly associated with PV only (odds ratio=2.16). For the phenotype-genotype intragene haplotype analyses, the EPOR intragene haplotypes GAAA and GGAA were significantly associated with PV (simulated global p-value = 0.058, simulated individual p-values 0.0013 and 0.0068, haplotype frequency of 35% and 56%, respectively). In addition to EPOR, 6 intragene haplotypes within JAK2 where significantly associated with PV (simulated global p-value &lt; 0.0001, individual simulated p-values &lt; 0.03). Conclusion: The current study demonstrates a genotype-phenotype association that involves JAK2 and EPOR in the setting of PV, but not that of AMM. Some JAK2 SNPs were found to be associated with both PV and ET but in opposite direction. Therefore, genetic variation among MPDs might contribute to phenotypic diversity in the presence of specific mutations.


1992 ◽  
Vol 263 (4) ◽  
pp. H1190-H1196 ◽  
Author(s):  
H. Nielsen ◽  
J. M. Hasenkam ◽  
H. K. Pilegaard ◽  
C. Aalkjaer ◽  
F. V. Mortensen

Human subcutaneous resistance arteries (122-298 microns), isolated from 139 patients undergoing surgery, were mounted in an isometric myograph. With the use of multiple regression analysis, five different modes of activation were examined for possible associations with age and mean arterial blood pressure of the patients: the contractile responses to 10 microM norepinephrine (mixed alpha 1-agonist/alpha 2-agonist), perivascular nerve stimulation, 10 microM phenylephrine (alpha 1-agonist), 100 microM B-HT 933 (alpha 2-agonist), and depolarization by potassium chloride. Blood pressure increased significantly with age. Blood pressure independently was not correlated to any mode of activation. With increasing patient age, however, responses to norepinephrine, phenylephrine, and perivascular nerve stimulation decreased, whereas the response to B-HT 933 increased; responses to potassium chloride were unaltered. Also corrected for changes in blood pressure, age independently was negatively correlated to the response to norepinephrine and phenylephrine, whereas a positive, though nonsignificant (P value = 0.12), correlation was observed between age independently and the response to B-HT 933. These data suggest that the ability of isolated human resistance arteries to evoke contractions medicated by postjunctional alpha 1-, but not alpha 2-adrenoceptors, decreases with age.


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