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Dec 2019 DOI 10.14302/issn.2326-0793.jpgr-19-3114
Ollomo BenjaminCorresponding author
Unité Mixte de Recherches (UMR-BIOMED), Faculté de Médecine, B.P 8507 Libreville, Gabon
Background During the last two decades, the polymorphism of Angiotensin-Converting Enzyme (ACE) gene has been extensively studied among different human populations. In humans, several studies have shown the relationship between this polymorphism and the risk of many serious diseases with a heavy burden of health in developing countries. After analyzing the polymorphism in the population, the present study was also concerned with the investigation of an eventual association between hypertension, stroke, cancer prostate and I/D polymorphism of the ACE gene. Materials and Methods Our study population included 163 Baka (pygmy) and 158 Fang (Bantu) from Gabon to evaluate the polymorphism in the country. Concerning the diseases, we included 105 patients and 120 controls for hypertension, 37 patients stroke matched with 50 controls and 97 patients with prostate cancer were recruited. All participants in the study were genotyped for the ACE I/D polymorphism obtained by polymerase chain reaction amplification on genomic DNA. Results Our analysis showed that the ACE D allele DD genotype frequencies were highest of all the data so far in human populations. We obtained a frequency of 0.138 for I allele and 0.862 for D allele among pygmy and the frequencies of 0.313 and 0.687 respectively for the I and D alleles. This difference was significant (p<0.05). In patients, we revealed the predominance of D allele and DD genotype for hypertension (0.27 for I allele and 0.73 for D allele), for stroke (0.15 for I allele and 0.85 for D allele) and 83% of individuals with cancer prostate carry the D allele. D allele and DD genotype are associated with risk to hypertension whereas allele I seem protective at the occurrence of stroke (p<0.05 between healthy and controls). Conclusion We show that the D allele and DD genotype were higher in this population. Also theses two signatures may be associated at genetic risk of hypertension, stroke and prostate cancer in this country deprived of human resources for quality care of many patients.
Aug 2019 DOI 10.14302/issn.2572-3030.jcgb-19-2597
Oluwafemi Oyamakin S.Corresponding author
Department of Statistics, University of Ibadan, Nigeria
In other to present a series of stochastic models from population dynamics capable of describing rudimentary aspects of genetic evolution, we studied two-allele Wright–Fisher and the Moran models for evolution of the relative frequencies of two alleles at a diploid locus under random genetic drift in a population of fixed size “simplest form, selection, and random mutation”. Principal results were presented in qualitative terms, illustrated by Monte Carlo simulations from R and http://www.radford.edu/~rsheehy/Gen_flash/popgen. Moran and the Wright-Fisher Models exhibited the same fixation probabilities, only that the Moran model runs twice as fast as the Wright-Fisher Model. A clue that can help us to understand this result is provided by the variance in reproductive success in the two models. Genetic changes due to drift were neither directional nor predictable in any deterministic way. Nonetheless, genetic drift led to evolutionary change in the absence of mutation (P=0.5), natural selection or gene flow. In general, alleles drift to fixation is significantly faster in smaller populations. Probability of fixation of an allele A was approximately equivalent to the initial frequency of that allele. With the inclusion of selection in our model, probability of fixation of a favoured allele due to natural selection increased with increase in fitness advantage and population size. The time taken to reach fixation is much slower, in case of no selective advantage, than a fixation under mutation with selective advantage.
Mar 2017
Remberger MatsCorresponding author
Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital,
This article examines how HLA‑DRB1 allele mismatching influences outcomes after hematopoietic stem cell transplantation. It reviews graft‑versus‑host disease risk, engraftment, and survival metrics in the context of donor matching strategies. The findings support careful allele‑level typing to optimize donor selection and improve post‑transplant prognosis.
Feb 2025 DOI 10.14302/issn.2326-0793.jpgr-25-5405
Ho Ming-FenCorresponding author
Alcohol use disorder (AUD) is the most prevalent substance use disorder. Excessive alcohol consumption leads to a range of health issues. We set out to identify inflammatory markers linked to alcohol consumption, which might ultimately offer novel insight into genetic underpinnings and have implications for alcohol-associated disease. Alcohol consumption and blood-based multi-omics data were collected by The Mayo Clinic Center for Individualized Treatment of Alcohol Dependence study. Plasma samples from patients with AUD were used for proteomics analysis using the OLINK “Explore Inflammation” panel (n=410). Liver enzymes were also measured. A genome-wide association study (GWAS) was performed to explore the relationship between genetic variants and plasma TREM2 levels. Our findings show thatplasma triggering receptor expressed on myeloid cells 2 (TREM2), a key gene associated with neurodegenerative disease, was the most significant signal correlated with alcohol consumption, and has also been associated with liver enzyme levels in patients with AUD. We identified the rs7232 single nucleotide polymorphism (SNP) in MS4A6A as a key genetic variant associated with plasma TREM2 levels, with the minor allele (A) linked to higher TREM2 levels and increased alcohol consumption, particularly in men. Furthermore, MA4A6A is an ethanol-responsive gene in a SNP-dependent manner, and the variant genotype of the rs7232 SNP was associated with lower expression for MA4A6A due to proteasome-mediated protein degradation. In summary, this study provides insight into the relationship between plasma TREM2 levels, alcohol consumption, and liver function in AUD patients, shedding light on genetic factors underlying alcohol-related diseases.
May 2020 DOI 10.14302/issn.2575-7881.jdrr-20-3343
Hussen Abdelrhman AmgedCorresponding author
Assis Professor, Department of Hematology and Immunohematology, Omdurman Islamic university / Sudan
Background Anemia of chronic disease is anemia found in certain chronic disease states, is typically marked by the disturbance of iron homeostasis or hypoferremia. Chronic renal failure is currently known as Chronic Kidney Disease (CKD) or Chronic Renal Insufficiency (CRI) implies long-standing, progressive and irreversible renal parenchyma disease resulting in diminished renal function up to 40 to 60%. Often, chronic kidney disease is diagnosed as a result of screening of people known to be at risk of kidney problems, such as those with high blood pressure or diabetes and those with a blood relative with chronic kidney disease. This disease may also be identified when it leads to one of its recognized complications such as cardiovascular disease, anemia, or pericarditis. Methods Sysmex kx21 used to CBC and the Cobase411 used to iron profile. Enzyme-Linked immunoassay (ELISA) was used to determine the level of serum hepcidin. Sample preparation and PCR detection of HAMP DNA Polymorphisms: Restriction digestion of PCR products was done using Fast Digest. (Figure 1). Results Serum hepcidin levels higher in patients with anemia of chronic kidney disease compared with healthy controls mean. The polymorphisms of the hepcidin gene promoter in Sudanese patients with ACKD showed that the hepcidin HAMP AA genotype 70, AG 23, and GG 7 in 100 patients dialysis-dependent and AA 83, AG 17 and GG 0, and the allele A are more frequent in patients affected by ACKD. Significant statistical association observed between the hepcidin level and end-stage kidney disease. Conclusion This study evaluates for the first time the association between anemia of chronic kidney disease and hepcidin genes promoter polymorphisms and show that the hepcidin HAMP AA genotype and the allele A are more frequent in patients affected by ACKD, further investigation is needed, our data support the hypothesis and hepcidin HAMP are important in the pathophysiology of ACKD.
Mar 2020 DOI 10.14302/issn.2374-9431.jbd-20-3195
E.G SergeevaCorresponding author
FIRST St. Petersburg state medical University named after academician I. P. Pavlov
Purpose The goals of the present study were to assess the genotypic and allelic distribution of Bsm-I (rs1544410) and Apa-I (rs7975232) polymorphisms of the vitamin D receptor (VDR) gene in coronary artery disease (CAD) patients in comparison to control patients of the same age without CAD and to determine whether these gene variants are associated with dyslipidemia. Materials and Methods Based on a case-control design, 302 hospitalized patients with CAD and 194 people of comparable age without CAD were enrolled in the study. The BsmI and ApaI polymorphisms of VDR gene were studied using polymerase chain reaction followed by restriction analysis. The allele digested by the restriction enzyme was denoted by a lower letter, whereas that not digested was indicated by a capital letter. Determination of the level of vitamin D and immunoreactive insulin in the blood serum was carried out using the immuno-enzyme method. Results The bb genotype of Bsm-I VDR gene polymorphism was detected more often in patients with CAD than in the comparison group with an increased risk of CAD by 1.52 times (p=0.006, OR=1.52(1.05÷2.2). The level of HDL cholesterol was higher in CAD patients − carriers of BB genotype compared to its level in Bb genotype carriers and bb genotype carriers (1,13±0,05 mmol/l, 1,01±0,03 mmol/l, 1,02±0,03 mmol/l respectively, p<0,05). The level of vitamin D was higher in patients with BB genotype compared to its level in bb genotype carriers (45.12±3.73 nmol / l and 34.16±1.95 nmol/l respectively, p=0.008). The occurrence of a allele of Apa-I VDR gene polymorphism was higher in patients with CAD than in the control group (p=0.02, OR=1.21(0.93÷1.57). HDL cholesterol level was higher in CAD patients - AA genotype carriers compared with carriers of Aa and aa genotypes (1.18±0.08 mmol / l, 1,02±0.02 mmol / l and 1.01±0.03 mmol/l respectively, p<0,05). Immunoreactive insulin level was significantly higher in CAD patients – aa genotype carriers. No differences in LDL cholesterol and triglycerides were found. Vitamin D level was lower in CAD patients - Aa and aa genotype carriers (33,8±33,9 nmol/l ,p=0,02 and 24,7±4,9 nmol/l, p=0,05 respectively in comparison to vitamin D level = 43,3 ±4,2 nmol/l in AA genotype carriers). Conclusion The bb genotype of Bsm-I VDR gene polymorphism is associated with an increased risk of CAD. A carriage of b allele in CAD patients is associated with lower level of vitamin D and HDL cholesterol. A carriage of a allele of Apa-I VDR gene polymorphism in CAD patients is associated with lower level of vitamin D and HDL cholesterol.
Mar 2020 DOI 10.14302/issn.2575-1212.jvhc-20-3234
di Virgilio FabrizioCorresponding author
DVM, Clinique Vétérinaire Vet24 – 59700 – Marcq en Baroeul, France
Aim of the Research The aim of this study is to analyze a group of dogs of different breeds affected by osteosarcoma (OSA), to document any prevalence of this primary bone neoplasia in breeds that are phylogenetically close and to help with further research human medicine, as a model of study for prevalence and epidemiology of human OSA in multiple populations. Study Design Pilot study from two canine surgery databases between 2002 and 2013. Materials and Methods Breeds were classified in groups based on their phylogenetical proximity. Differences in prevalence of OSA between breeds and groups were evaluated with a permutation test. For each breed and each group, a ranking was made by calculating 95 % confidence intervals and counting the no-overlapping between breeds and groups. The relation between the dogs’ heights and the prevalence of OSA was analyzed using a logistic regression between the disease status and dog size. Results A total of 67 dogs with OSA, in 26 different breeds were included. Ten breeds were overrepresented and, the majority of these, were classified in 2 predisposed groups phylogenetically close to each other. The prevalence of OSA was associated with the dogs’ height within predisposed breeds, but, in general, taller breeds were not the most affected. Conclusions and Clinical Relevance In this study, despite the small number of dogs, we observed that the most commonly affected breeds with OSA are phylogenetically closely related. This highlights the importance of genetics in the aetiology of canine OSA . In this preliminary study, indications are given on breeds, samples and genome locations to be further investigated. This could allow identification of pathogenic alleles in dogs, and potentially in humans. Furthermore this pilot research can represent a model of epidemiologic study of human OSA.
Mar 2020 DOI 10.14302/issn.2694-1198.jge-20-3206
Volobuev A.N.Corresponding author
Samara State Medical University. Department of Medical Physics. Samara, Russia
On the basis of Hardy – Weinberg’s law the problem of inbreeding in a family tree and a population was investigated. With use of an inbreeding factor are received the discrete equation for a family tree and differential equation for a population. The numerical solution of the differential equation for a population was found and analyzed at various values of the inbreeding factor. Migration of inbred population is investigated in view of natural selection. It was shown that velocity of migration falls with increase of the inbreeding factor. Interrelation of the recessive allele frequency at woman for a migrating population with inbreeding factor and standard parameter of selection was found.
Dec 2019 DOI 10.14302/issn.2694-1198.jge-19-3079
Volobuev A.N.Corresponding author
Samara State Medical University, Department of Medical Physics, Samara, Russia
The problem of natural selection against recessive homozygotes in a population is investigated. It is shown that natural selection of mutant alleles linked with the Х-chromosome in a population at women is described by the nonlinear differential equation of the third order. The order of the differential equation characterizes a power of selection. It is marked that the high order of the differential equation of natural selection allows level all mutational processes in Earth populations.
Jun 2019 DOI 10.14302/issn.2374-9431.jbd-19-2788
Sergeeva E.G.Corresponding author
First Pavlov State Medical University of St. Petersburg
Purpose The goal of this study is to determine the association of L162V polymorphism of PPAR-alpha gene, A603G polymorphism of tissue factor gene and the risk of coronary heart disease development in Russian population. Materials and Methods A clinical and genetic study of 414 patients with CHD and 220 people of comparable age without CHD which amounted to a control group was performed. L162L and L162V genotypes of L162V polymorphism of PPAR-α gene, A603A, A603G and G603G genotypes of A603G polymorphism of tissue factor gene were determined by polymerase chain reaction followed by restriction analysis. Results A carriage of L162V genotype and V allele of PPAR-α gene was associated with an increase risk of CHD in 2,13 times (L162V genotype) and in 2,21 times (V allele), with an increase in risk of CHD before the age of 45 years in 4,68 times (L162V genotype) and in 3,88 times (V allele). Significantly higher in patients with CHD compared with the general population and in patients with a carriage of G603G genotype and G allele of tissue factor gene was associated with the increase of CHD risk in 2,68 times (G603G genotype) and in 4,37 times (G allele), occurred more frequently in patients with debut of disease at age of 45 years and younger. The level of tissue factor was significantly higher in patients with CHD – carriers G603G genotype compared with carriers A603A genotype (217,9±15,2 pg/ml and 152,6±30,4 pg/ml, respectively, p=0,04). A carriage of the combination of L162V and G603G genotypes was associated with an increased risk of CHD in 3,04 times. Conclusion A carriage of V allele of L162V polymorphism of PPAR-α gene and G allele of A603G polymorphism of tissue factor gene, as well as their pair combination are associated with an increased CHD risk, especially at age 45 years or less.
Feb 2019 DOI 10.14302/issn.2379-7835.ijn-19-2585
Chen Di-YunCorresponding author
Guangdong Provincial Key Laboratory for Radionuclides Pollution Control and Resources, School of Environmental Science and Engineering, Guangzhou University, Guangzhou-510006, China.
With the possibility of the Water-Energy-Food (WEF) Nexus since a long time back, overlooked interlinkages between WEF are getting the chance to be indisputable. Nonetheless, agriculture is responsible for quite a bit of fresh water over-use. Food production further effects the water and energy sectors through degradation of land, changes in overflow, disturbance of groundwater release, water quality, accessibility of water and land for different purposes. The responsibilities of this unparalleled issue include particular parts of the organization around the Nexus. While a couple of papers try to conceptualize the Nexus-Governance, this phenomenal report gives a rich combination of work for further WEF-Nexus ponders and integrative methodologies.
Jun 2017 DOI 10.14302/issn.2576-9359.jot-17-1603
Caprara CarlottaCorresponding author
Department of Nephrology, Dialysis and Transplantation; International Renal Research Institute Vicenza (IRRIV); San Bortolo Hospital; Vicenza.
Single-nucleotide polymorphisms (SNPs) in genes involved in immune responses and in the pharmacokinetics/pharmacodynamics of immunosuppressive drugs influence transplant outcomes of patients receiving the same immunosuppressive therapy. The aim of our preliminary study was to determine the SNPs profiles of ABCB1/MDR-1, UGT1A9, IMPDH2, IL-10 and TNF-α genes associated with acute rejection (AR) events in renal allograft recipients. DNA was extracted from whole blood samples of 220 individuals in 3 experimental groups; Case: 41 kidney transplant patients with AR event(s), Control I: 109 kidney transplant patients without AR event, Control II: 70 healthy blood donors. Acute rejection defined as rapid, unexplained rise in serum creatinine was biopsy-proven. 19 SNPs were analyzed by Sanger Sequencing. Analysis of allele and genotype frequencies and gene-disease association tests were performed. Allele frequencies of healthy persons are in line with ones reported from Europe indicating that the studied population is representative. Statistically significant differences only by the comparison of kidney transplant patients with AR event(s) and healthy individuals are found for rs2032582 and rs1045642 SNPs of ABCB1/MDR1, the latter is also not in Hardy-Weinberg equilibrium in our population. Patients with specific alleles for these SPNs are more prone to have acute rejection events. Certain allele variants of ABCB1/MDR1 by modifying the effectiveness of the drugs may compromise the success of the immunosuppressive therapy and put patients at higher risk to reject the new organ. Therefore screening for these polymorphisms before transplantation would help clinicians to more accurately personalize medications.
Jun 2016
Ratan Bandyopadhyay ArupCorresponding author
Department of Anthropology, University College of Science, Technology & Agriculture, University of Calcutta, India
Earlier studies reported significant association of obesity, hypertension and Type2 Diabetes Mellitus (T2DM). Genetic and many disease-associated alleles have been identified through GWAS and applied to T2DM and indicated roles of renin-angiotensin system (RAS) in insulin signaling pathway and insulin resistance has been well documented. Angiotensin converting enzyme (ACE) gene catalyzes the conversion of angiotensin I to angiotensin II and also inactive the vasodilatation and hence renin-angiotensin system (RAS) in insulin signaling pathway and insulin resistance has been reported. To best of the knowledge we are reporting for the first time regarding association of ACE gene polymorphism with body composition, physiological and metabolic variables among any endogamous ethnic group (Kurmis) from of West Bengal, Eastern India. To achieve the purpose, total 197 (male 99 and female 98) randomly selected apparently healthy unrelated adult individuals of Kurmi population of Purulia District, West Bengal, India were incorporated in the present study. Anthropometric variables, physiological variables (blood pressure) and metabolic variables (PP blood sugar) have been collected using standard techniques. Extracted genomic DNA was PCR amplified and genotyped to understand ACE gene I/D polymorphism. The result demonstrated significant (p<0.05) sexual dimorphism in PBF. MAP and PP blood sugar found to be in normal range among the Kurmis. ACE gene polymorphism showed no deletion of the Kurmis and hence, only the prevalence of ACE II (insertion-Insertion) genotype has been noticed. The present study vindicated on the basis of body composition in terms of fat patterning, physiological and metabolic variables and ACE gene polymorphism that there is very low or no risk of T2DM among the Kurmis of West Bengal, India.
Feb 2016 DOI 10.14302/issn.2374-9431.jbd-15-890
E. Buroker NormanCorresponding author
Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
Purpose Signal Transducer and Activator of Transcription 4 (STAT4) is important for signaling by interleukins (IL-12 and IL-23) and type 1 interferons and has been found to have several simple nucleotide polymorphisms (SNPs) associated with human disease. STAT4 SNPs were computationally examined with respect to changes in potential transcriptional factor binding sites (TFBS) and these changes were discussed in relation to human disease. Methods The JASPAR CORE and ConSite databases were instrumental in identifying the TFBS. The Vector NTI Advance 11.5 computer program was employed in locating all theTFBS in theSTAT4 gene from 4 kb upstream of the transcriptional start site to 8.3 kb past the 3’UTR. The JASPAR CORE database was also involved in computing each nucleotide occurrence (%) within the TFBS. Results The STAT4 SNPs in the 70 kb intron between exon 2 and 3 are in linkage disequilibrium and have previously been found to be significantly associated with several vasculitis diseases as well as diabetes. The SNP alleles were found to alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in TFBS and thereby, alter which transcriptional factors potentially regulate the STAT4 gene. These STAT4 SNPs should be considered as regulatory (r) SNPs. Conclusion The alleles of each rSNP were found to generate unique TFBS resulting in potential changes in TF STAT4 regulation. These regulatory changes were discussed with respect to changes in human health that result in disease.
Feb 2016 DOI 10.14302/issn.2326-0793.jpgr-15-889
E. Buroker NormanCorresponding author
Department of Pediatrics, University of Washington, Seattle, WA 98195, USA
Purpose The endothetal Per-Arnt-Sim (PAS) domain protein 1 (EPAS1) gene which encodes hypoxia-inducible-factor-2 alpha (HIF2a) is a transcription factor that is involved in the response to hypoxia. EPAS1 has been found to have four (rs56721780, rs6756667, rs7589621, rs1868092) simple nucleotide polymorphisms (SNPs) associated with human disease.These SNPs were computationally examined with respect to changes in potential transcriptional factor binding sites (TFBS) and these changes were discussed in relation to disease and alterations in high altitude adaptation in humans. Methods The JASPAR CORE and ConSite databases were instrumental in identifying the TFBS. The Vector NTI Advance 11.5 computer program was employed in locating all theTFBS in theEPAS1 gene from 1.6 kb upstream of the transcriptional start site to 539 bps past the 3’UTR. The JASPAR CORE database was also involved in computing each nucleotide occurrence (%) within the TFBS. Results The EPAS1 SNPs in the promoter, intron two and the 3’UTR regions have previously been found to be significantly associated with disease and different levels of high-altitude hypoxia among native Tibetans. The SNP alleles were found to alter the DNA landscape for potential transcriptional factors (TFs) to attach resulting in changes in TFBS and thereby, alter which transcriptional factors potentially regulate the EPAS1 genesuch as for the glucocorticoid and mineralocorticoid nuclear receptor binding sites created by the rs7589621 rSNP EPAS1-G allele. These receptors regulate carbohydrate, protein and fat metabolism. Also the minor rs7589621 rSNP EPAS1-A creates a punitive TFBS for the FOXC TF which is an important regulator of cell viability and resistance to oxidative stress. These EPAS1 SNPs should be considered as regulatory (r) SNPs. Conclusion The alleles of each rSNP were found to generate unique TFBS resulting in potential changes in TF EPAS1 regulation. The punitive changes in TFBS created by the four rSNPs could very well influence the significant cline in allele frequencies seen in Tibetans with increasing altitude or the haplotype association with high altitude polycythemia in male Han Chinese. These regulatory changes were discussed with respect to changes in human health that result in disease and sickness.