scholarly journals Genetic variants associated with skin photosensitivity in a southern European population from Spain

2018 ◽  
Vol 34 (6) ◽  
pp. 415-422 ◽  
Author(s):  
Barbara Hernando ◽  
Elena Sanz-Page ◽  
Gerard Pitarch ◽  
Laura Mahiques ◽  
Francisca Valcuende-Cavero ◽  
...  
Keyword(s):  
Genetic Variants ◽  
European Population ◽  
Skin Photosensitivity

scholarly journals Evaluation of the Influence of Genetic Variants of SLC2A9 (GLUT9) and SLC22A12 (URAT1) on the Development of Hyperuricemia and Gout

2020 ◽  
Vol 9 (8) ◽  
pp. 2510
Author(s):  
Katerina Pavelcova ◽  
Jana Bohata ◽  
Marketa Pavlikova ◽  
Eliska Bubenikova ◽  
Karel Pavelka ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Uric Acid ◽  
Genetic Variants ◽  
Biochemical Parameters ◽  
Previous Analysis ◽  
Direct Sequencing ◽  
Low Frequency ◽  
European Population ◽  
The Body ◽  
Genes Encoding

Urate transporters, which are located in the kidneys, significantly affect the level of uric acid in the body. We looked at genetic variants of genes encoding the major reabsorption proteins GLUT9 (SLC2A9) and URAT1 (SLC22A12) and their association with hyperuricemia and gout. In a cohort of 250 individuals with primary hyperuricemia and gout, we used direct sequencing to examine the SLC22A12 and SLC2A9 genes. Identified variants were evaluated in relation to clinical data, biochemical parameters, metabolic syndrome criteria, and our previous analysis of the major secretory urate transporter ABCG2. We detected seven nonsynonymous variants of SLC2A9. There were no nonsynonymous variants of SLC22A12. Eleven variants of SLC2A9 and two variants of SLC22A12 were significantly more common in our cohort than in the European population (p = 0), while variants p.V282I and c.1002+78A>G had a low frequency in our cohort (p = 0). Since the association between variants and the level of uric acid was not demonstrated, the influence of variants on the development of hyperuricemia and gout should be evaluated with caution. However, consistent with the findings of other studies, our data suggest that p.V282I and c.1002+78A>G (SLC2A9) reduce the risk of gout, while p.N82N (SLC22A12) increases the risk.

scholarly journals Genotype–phenotype correlation of 17 cases of Pompe disease in Spanish patients and identification of 4 novel GAA variants

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Paula Hernández-Arévalo ◽  
José D. Santotoribio ◽  
Rocío Delarosa-Rodríguez ◽  
Antonio González-Meneses ◽  
Salvador García-Morillo ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Genetic Variants ◽  
European Population ◽  
Exercise Intolerance ◽  
Phenotype Correlation ◽  
Pathogenic Variants ◽  
Genotype Phenotype Correlation ◽  
C 32 ◽  
Generation Sequencing ◽  
Worse Prognosis

Abstract Background Pompe disease (PD) is an autosomal recessive metabolic disorder caused by pathogenic variants in the acid α-glucosidase gene (GAA) that produces defects in the lysosomal acid α-1,4-glucosidase. We aimed to identify genetic variations and clinical features in Spanish subjects to establish genotype–phenotype correlation. Methods A total of 2637 samples of patients who showed symptoms or susceptible signs of PD were enrolled in this observational study. Enzymatic activity was detected by fluorometric techniques and the genetic study was carried out using Next-Generation Sequencing. Results Fourteen different variants from 17 diagnosed patients were identified, seven males and nine females with LOPD (mean age 36.07, SD 20.57, range 7–64) and a 2-day-old boy with IOPD, four genetic variants had not been described in the literature previously, including a homozygous variant. In all of them α-glucosidase activity was decreased. Muscle weakness, respiratory distress, exercise intolerance, hypotonia, dysphagia and myalgia were commonly observed in patients. Conclusions This study report four new genetic variants that contribute to the pathogenic variants spectrum of the GAA gene. We confirm that patients in Spain have a characteristic profile of a European population, with c.-32-13T>G being the most prevalent variant. Furthermore, it was confirmed that the c.236_246delCCACACAGTGC pathogenic variant in homozygosity is associated with early disease and a worse prognosis.

scholarly journals A Genome-Wide Association Study of spontaneous preterm birth in a European population

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 255 ◽  
Author(s):  
Wilfred Wu ◽  
Erin A S Clark ◽  
Tracy A Manuck ◽  
M Sean Esplin ◽  
Michael W Varner ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Genetic Variants ◽  
Association Studies ◽  
European Population ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Spontaneous Preterm Birth ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk

Background: Preterm birth is defined as a birth prior to 37 completed weeks’ gestation. It affects more than 10% of all births worldwide, and is the leading cause of neonatal mortality in non-anomalous newborns. Even if the preterm newborn survives, there is an increased risk of lifelong morbidity. Despite the magnitude of this public health problem, the etiology of spontaneous preterm birth is not well understood. Previous studies suggest that genetics is an important contributing factor. We therefore employed a genome-wide association approach to explore possible fetal genetic variants that may be associated with spontaneous preterm birth.Methods: We obtained preterm birth phenotype and genotype data from the National Center for Biotechnology Information Genotypes and Phenotypes Database (study accession phs000103.v1.p1). This dataset contains participants collected by the Danish National Birth Cohort and includes 1000 preterm births and 1000 term births as controls. Whole genomes were genotyped on the Illumina Human660W-Quad_v1_A platform, which contains more than 500,000 markers. After data quality control, we performed genome-wide association studies for the 22 autosomal chromosomes.Results: No single nucleotide polymorphism reached genome-wide significance after Bonferroni correction for multiple testing.Conclusion: We found no evidence of genetic association with spontaneous preterm birth in this European population. Approaches that facilitate detection of both common and rare genetic variants, such as evaluation of high-risk pedigrees and genome sequencing, may be more successful in identifying genes associated with spontaneous preterm birth.

scholarly journals SARS-CoV-2 susceptibility and ACE2 gene variations within diverse ethnic backgrounds

2021 ◽  
Author(s):  
Nirmal Vadgama ◽  
Alexander Kreymerman ◽  
Jackie Campbell ◽  
Olga Shamardina ◽  
Christiane Brugger ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Disease Susceptibility ◽  
Ethnically Diverse ◽  
European Population ◽  
East Asians ◽  
Receptor Affinity ◽  
The United Kingdom ◽  
Ethnic Comparisons ◽  
Protein Variants ◽  
Ace2 Gene

Background Host genetics play a major role in COVID-19 susceptibility and severity. Here, we analyse an ethnically diverse cohort of National Health Service (NHS) patients in the United Kingdom (UK) to assess the association between variants in the ACE2 locus and COVID-19 risk. Methods We analysed whole-genome sequencing (WGS) data of 6,274 participants who were tested for SARS-CoV-2 from the UK's 100,000 Genomes Project (100KGP) for the presence of ACE2 variants and expression quantitative trait loci (eQTLs). Findings We identified a splice site variant (rs2285666) associated with increased ACE2 expression with an overrepresentation in SARS-CoV-2 positive patients relative to 100KGP controls (p = .015), and in hospitalised European patients relative to outpatients in intra-ethnic comparisons (p = .029). We also compared the prevalence of 288 eQTLs, of which 23 were enriched in SARS-CoV-2 positive patients. The eQTL rs12006793 had the largest effect size (d = 0.91), which decreases ACE2 expression and is more prevalent in controls, thus potentially reducing risk of COVID-19. We identified three novel nonsynonymous variants predicted to alter ACE2 function, and showed that three variants (p.K26R, p.H378R, p.Y515N) alter receptor affinity for the viral Spike (S) protein. Variants p.K26R and p.N720D are more prevalent in the European population (p < .001), but Y497H is less prevalent compared to East Asians (p = .020). Interpretation Our results demonstrate that the spectrum of genetic variants in ACE2 may inform risk stratification of COVID-19 patients and could partially explain the differences in disease susceptibility and severity among different ethnic groups. Funding The 100KGP is funded by the National Institute for Health Research and NHS England. Funding was also obtained from Stanford University, Palo Alto.

scholarly journals POS1142 INTERLEUKIN-37: ASSOCIATIONS OF PLASMA LEVELS AND GENETIC VARIANTS IN GOUT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 850.2-851
Author(s):  
A. Navrátilová ◽  
V. Voclonová ◽  
H. Hulejova ◽  
L. Andres Cerezo ◽  
J. Zavada ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Plasma Levels ◽  
European Population ◽  
Enzyme Linked Immunosorbent Assay ◽  
Acute Gout ◽  
Tophaceous Gout ◽  
Control Subjects ◽  
Primary Gout ◽  
Anti Inflammatory ◽  
Gout Flare

Background:IL-37, recently characterized IL-1 family member, has anti-inflammatory effects by suppression of IL-1ß and other proinflammatory cytokines. In this study we investigated the effects of genetics variants in IL-37 link with IL-37 plasma levels in a cohorts of patients with hyperuricemia/gout.Objectives:The aim of this study was to determine the association of IL-37 gene polymorphism and plasma IL-37 levels in patients with hyperuricemia and gout.Methods:The cohorts consisted of 50 control subjects, 50 subjects of primary hyperuricemia, 50 subjects of primary gout, 28 subjects of tophaceous gout and 19 subjects of acute gout flare. The analyzed cohorts were selected from a previously reported set of 250 hyperuricemia/gout patients and 132 normouricemic subjects (1) according to the descending level of serum urate. All coding regions and intron-exon boundaries of IL-37, exon 1-5, were amplified and sequenced directly. Comparisons of presence/absence of identified variants was performed using P-values binomial test. Levels of plasma IL-37 were measured using Enzyme-Linked ImmunoSorbent Assay. All tests were performed in accordance with standards set by the institutional ethics committees, which approved the project in Prague (no.6181/2015).Results:We identified 12 IL-37 genetic variants: five intron (rs28947188, rs2466448, rs3811045, rs3811048, rs2708944), and seven non-synonymous allelic variants (rs3811046, rs3811047, rs2708943, rs2723183, rs2723187, rs2708947, rs27231927). Minor allele frequency (MAF) of those variants in European population from ExAC databases were used for comparison. Our data showed that the rs28947188, rs3811045, rs3811046, rs3811047, rs2723187, rs2708947, and rs27231927 variants were under-represented in the Czech hyperuricemia, gout, and tophaceous gout cohort compared with the control cohort and general European population (P = 0.0082 – 0.0395).The levels of plasma IL-37 were significantly higher in patients with tophaceous gout compared to control subjects (P 0.0329) whereas no changes were observed in subjects with primary hyperuricemia, primary gout or acute gout flare compared to control subjects. However, IL-37 was elevated in cohorts of patients with gout, tophaceous gout and acute gout flare compared to primary hyperuricemia subjects (P 0.0198, 0.0005, 0.0099; respectively).Conclusion:Although further analyzes are needed to elucidate the role of IL-37 in the gout, our results show that genetic variants in anti-inflammatory cytokine IL-37 are probably implicated in the pathogenesis of gout.References:[1]Toyoda Y, et al. Functional characterization of clinically-relevant rare variants in ABCG2 identified in a gout and hyperuricemia cohort. Cells. 2019 Apr 18;8(4).Acknowledgements:This study was supported by the grant from the Czech Republic Ministry of Health RVO 00023728.Disclosure of Interests:None declared.

Genetic variants in RELN are associated with otosclerosis in a non-European population from Tunisia

2010 ◽  
Vol 74 (5) ◽  
pp. 399-405 ◽  
Author(s):  
Ayda Khalfallah ◽  
Isabelle Schrauwen ◽  
Malek Mnaja ◽  
Erik Fransen ◽  
Imed Lahmar ◽  
...  
Keyword(s):  
Genetic Variants ◽  
European Population

scholarly journals Predictive Ability of a Clinical-Genetic Risk Score for Venous Thromboembolism in Northern and Southern European Populations

TH Open ◽  
2021 ◽  
Vol 05 (03) ◽  
pp. e303-e311
Author(s):  
Eduardo Salas ◽  
Maria Farm ◽  
Sara Pich ◽  
Liselotte Onelöv ◽  
Kevin Guillen ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Factor V Leiden ◽  
European Population ◽  
Factor V ◽  
Allelic Frequencies ◽  
Northern European ◽  
Auc Value ◽  
European Populations

AbstractVenous thromboembolism (VTE) is a complex, multifactorial problem, the development of which depends on a combination of genetic and acqfiguired risk factors. In a Spanish population, the Thrombo inCode score (or TiC score), which combines clinical and genetic risk components, was recently proven better at determining the risk of VTE than the commonly used model involving the analysis of two genetic variants associated with thrombophilia: the Factor V Leiden (F5 rs6025) and the G20210A prothrombin (F2 rs1799963).The aim of the present case–control study was to validate the VTE risk predictive capacity of the TiC score in a Northern European population (from Sweden).The study included 173 subjects with VTE and 196 controls. All were analyzed for the genetic risk variants included in the TiC gene panel. Standard measures —receiver operating characteristic (ROC) area under the curve (AUC), sensitivity, specificity, and odds ratio (OR)—were calculated.The TiC score returned an AUC value of 0.673, a sensitivity of 72.25%, a specificity of 60.62%, and an OR of 4.11. These AUC, sensitivity, and OR values are all greater than those associated with the currently used combination of genetic variants. A TiC version adjusted for the allelic frequencies of the Swedish population significantly improved its AUC value (0.783).In summary, the TiC score returned more reliable risk estimates for the studied Northern European population than did the analysis of the Factor V Leiden and the G20210A genetic variations in combination. Thus, the TiC score can be reliably used with European populations, despite differences in allelic frequencies.

Biomarkers for afrophic chronic gastritis diagnosis in a dyspeptic european population

2001 ◽  
Vol 120 (5) ◽  
pp. A607-A607
Author(s):  
N BROUTET ◽  
M PLEBANI ◽  
C SAKAROVITCH ◽  
P SIPPONEN
Keyword(s):  
Chronic Gastritis ◽  
European Population
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