scholarly journals New insight on the Xq28 association with systemic sclerosis

2013 ◽  
Vol 72 (12) ◽  
pp. 2032-2038 ◽  
Author(s):  
F David Carmona ◽  
M Carmen Cénit ◽  
Lina-Marcela Diaz-Gallo ◽  
Jasper C A Broen ◽  
Carmen P Simeón ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Systemic Sclerosis ◽  
Meta Analysis ◽  
Conditional Logistic Regression ◽  
Statistical Significance ◽  
The Other ◽  
Nucleotide Polymorphisms ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Conditional Logistic Regression Analysis

ObjectiveTo evaluate whether the systemic sclerosis (SSc)-associated IRAK1 non-synonymous single-nucleotide polymorphism rs1059702 is responsible for the Xq28 association with SSc or whether there are other independent signals in the nearby methyl-CpG-binding protein 2 gene (MECP2).MethodsWe analysed a total of 3065 women with SSc and 2630 unaffected controls from five independent Caucasian cohorts. Four tag single-nucleotide polymorphisms of MECP2 (rs3027935, rs17435, rs5987201 and rs5945175) and the IRAK1 variant rs1059702 were genotyped using TaqMan predesigned assays. A meta-analysis including all cohorts was performed to test the overall effect of these Xq28 polymorphisms on SSc.ResultsIRAK1 rs1059702 and MECP2 rs17435 were associated specifically with diffuse cutaneous SSc (PFDR=4.12×10−3, OR=1.27, 95% CI 1.09 to 1.47, and PFDR=5.26×10−4, OR=1.30, 95% CI 1.14 to 1.48, respectively), but conditional logistic regression analysis showed that the association of IRAK1 rs1059702 with this subtype was explained by that of MECP2 rs17435. On the other hand, IRAK1 rs1059702 was consistently associated with presence of pulmonary fibrosis (PF), because statistical significance was observed when comparing SSc patients PF+ versus controls (PFDR=0.039, OR=1.30, 95% CI 1.07 to 1.58) and SSc patients PF+ versus SSc patients PF− (p=0.025, OR=1.26, 95% CI 1.03 to 1.55).ConclusionsOur data clearly suggest the existence of two independent signals within the Xq28 region, one located in IRAK1 related to PF and another in MECP2 related to diffuse cutaneous SSc, indicating that both genes may have an impact on the clinical outcome of the disease.

scholarly journals Novel identification of the IRF7 region as an anticentromere autoantibody propensity locus in systemic sclerosis

2011 ◽  
Vol 71 (1) ◽  
pp. 114-119 ◽  
Author(s):  
F David Carmona ◽  
Ramana Gutala ◽  
Carmen P Simeón ◽  
Patricia Carreira ◽  
Norberto Ortego-Centeno ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Conditional Logistic Regression ◽  
Statistical Significance ◽  
Genomic Region ◽  
Nucleotide Polymorphisms ◽  
Allelic Discrimination ◽  
Autoantibody Production

ObjectiveSystemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are related chronic autoimmune diseases of complex aetiology in which the interferon (IFN) pathway plays a key role. Recent studies have reported an association between IRF7 and SLE which confers a risk to autoantibody production. A study was undertaken to investigate whether the IRF7 genomic region is also involved in susceptibility to SSc and the main clinical features.MethodsTwo case-control sets of Caucasian origin from the USA and Spain, comprising a total of 2316 cases of SSc and 2347 healthy controls, were included in the study. Five single nucleotide polymorphisms (SNPs) in the PHRF1-IRF7-CDHR5 locus were genotyped using TaqMan allelic discrimination technology. A meta-analysis was performed to test the overall effect of these genetic variants on SSc.ResultsFour out of five analysed SNPs were significantly associated with the presence of anticentromere autoantibodies (ACA) in the patients with SSc in the combined analysis (rs1131665: pFDR=6.14 × 10−4, OR=0.78; rs4963128: pFDR=6.14 × 10−4, OR=0.79; rs702966: pFDR=3.83 × 10−3, OR=0.82; and rs2246614: pFDR=3.83 × 10−3, OR=0.83). Significant p values were also obtained when the disease was tested globally; however, the statistical significance was lost when the ACA-positive patients were excluded from the study, suggesting that these associations rely on ACA positivity. Conditional logistic regression and allelic combination analyses suggested that the functional IRF7 SNP rs1131665 is the most likely causal variant.ConclusionsThe results show that variation in the IRF7 genomic region is associated with the presence of ACA in patients with SSc, supporting other evidence that this locus represents a common risk factor for autoantibody production in autoimmune diseases.

scholarly journals The role of certain genetic polymorphism in development of sudden cardiac death in the Trans-Baikal Territory

2021 ◽  
pp. 35-42
Author(s):  
D.N. Zaitsev ◽  
◽  
P.V. Vasilenko ◽  
A.V. Govorin ◽  
E.A. Vasilenko ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Single Nucleotide Polymorphism ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Statistical Significance ◽  
Control Group ◽  
Study Group ◽  
Nucleotide Polymorphisms ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

Aim of the study. To study genetic polymorphisms rs10798 KCNQ1, rs3010396 CASQ2, rs20455 KIF6, rs2298566 SNX19, rs12143842 NOS1AP of subjects who died due to sudden cardiac death in Trans-Baikal Territory. Material and Methods. Over the period of 2017-2020, a total of 2211 autopsy protocols of subjects who died due to SCD were analysed. Th ese patient constituted the 1st study group (n=113). The control group consisted of healthy volunteers (n=70). The groups were comparable in age and gender. Molecular and genetic typing of the studied genes was performed. Results. The CC genotype of the single-nucleotide polymorphism rs3010396 CASQ2 showed statistical signifi cance in comparison with the control group(the chi-squared=26.95, df=2, p=0.001). The TT genotype was predominant in the control group amounting to 60% against 19.5% in the study group. Single-nucleotide polymorphism rs2298566 of gene SNX19 was also observed to be of statistical significance in the group of subjects who died from myocardial infarction. In the group of patients with SCD, rs20455 KIF6 and rs12143842 NOS1AP were of signifi cance along with rs3010396 CASQ2. Conclusion. Single-nucleotide polymorphism rs3010396 of the CASQ2 gene can be a predictor of sudden cardiac death, since in the 1st study group with this genotype showed its statistical signifi cance in all nosological groups. However, in the group, in which sudden cardiac death (cases coded I46.1 according to ICD-10) was indicated as the fi nal diagnosis, in addition to their statistical signifi cance single-nucleotide polymorphisms of the gene KIF6 rs20455, rs12143842 NOS1AP gene were noted; in the group where the cause of death was myocardial infarction, rs2298566 SNX19 gene polymorphism had statistical signifi cance. The results obtained make it possible to consider these polymorphisms as possible predictors of sudden cardiac death in the population of the Trans-Baikal Territory.

scholarly journals Association between rs12252 and influenza susceptibility and severity: an updated meta-analysis

2018 ◽  
Vol 147 ◽  
Author(s):  
T. Chen ◽  
M. Xiao ◽  
J. Yang ◽  
Y. K. Chen ◽  
T. Bai ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Strong Association ◽  
Dominant Model ◽  
Healthy Individuals ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Model C ◽  
Allelic Model

AbstractIn several lately published studies, the association between single-nucleotide polymorphism (SNP, rs12252) of IFITM3 and the risk of influenza is inconsistent. To further understand the association between the SNP of IFITM3 and the risk of influenza, we searched related studies in five databases including PubMed published earlier than 9 November 2017. Ten sets of data from nine studies were included and data were analysed by Revman 5.0 and Stata 12.0 in our updated meta-analysis, which represented 1365 patients and 5425 no-influenza controls from four different ethnicities. Here strong association between rs12252 and influenza was found in all four genetic models. The significant differences in the allelic model (C vs. T: odds ratio (OR) = 1.35, 95% confidence interval (CI) (1.03–1.79), P = 0.03) and homozygote model (CC vs. TT: OR = 10.63, 95% CI (3.39–33.33), P < 0.00001) in the Caucasian subgroup were discovered, which is very novel and striking. Also novel discoveries were found in the allelic model (C vs. T: OR = 1.37, 95% CI (1.08–1.73), P = 0.009), dominant model (CC + CT vs. TT: OR = 1.48, 95% CI (1.08–2.02), P = 0.01) and homozygote model (CC vs. TT: OR = 2.84, 95% CI (1.36–5.92), P = 0.005) when we compared patients with mild influenza with healthy individuals. Our meta-analysis suggests that single-nucleotide T to C polymorphism of IFITM3 associated with increasingly risk of severe and mild influenza in both Asian and Caucasian populations.

scholarly journals SNP rs2596542G>A in MICA is associated with risk of hepatocellular carcinoma: a meta-analysis

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Haichuan Wang ◽  
Hui Cao ◽  
Zhong Xu ◽  
Dong Wang ◽  
Yong Zeng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Single Nucleotide Polymorphism ◽  
Web Of Science ◽  
Meta Analysis ◽  
Genetic Models ◽  
Complex Class ◽  
Related Gene ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Histocompatibility Complex

Abstract The association of major histocompatibility complex class I chain-related gene A (MICA) single nucleotide polymorphism (SNP) rs2596542G>A and hepatocellular carcinoma (HCC) has been broadly studied, with inconsistent results. Therefore, we conducted the current meta-analysis to better elucidate the roles of SNP rs2596542G>A in HCC. Eligible articles were searched in PubMed, CNKI, Wanfang, Embase, VIP, Web of Science, and CBM databases up to November 2018. Odds ratios (ORs) and 95% CIs were applied. A total of 11 articles, including 4528 HCC patients and 16,625 control subjects, were analyzed. Results revealed that rs2596542G>A was significantly associated with HCC in the heterozygote (G/A versus A/A, P=0.006, OR = 0.854; 95% CI: 0.763–0.956); and dominant (G/G + G/A versus A/A; P=0.021; OR = 0.796; 95% CI: 0.655–0.967) genetic models. Nevertheless, we also detected significant associations between rs2596542G>A and HCV-induced HCC. Additionally, according to our analyses, SNP rs2596542G>A was not correlated with HBV-induced HCC. In conclusion, our findings suggest that MICA SNP rs2596542G>A is associated with HCC susceptibility amongst the Asian, Caucasian, and African ethnicity in certain genetic models. Specifically, MICA SNP rs2396542G>A is associated with risk of HCV-induced HCC, not HBV-induced HCC.

Analysis of Additional Virulence Genes and Virulence Gene Regions in Listeria monocytogenes Confirms the Epidemiologic Relevance of Multi-Virulence-Locus Sequence Typing

2008 ◽  
Vol 71 (12) ◽  
pp. 2559-2566 ◽  
Author(s):  
SARA LOMONACO ◽  
YI CHEN ◽  
STEPHEN J. KNABEL
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Listeria Monocytogenes ◽  
Virulence Genes ◽  
Virulence Gene ◽  
The Other ◽  
Evolutionary Divergence ◽  
Gene Sequences ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Molecular Subtyping

Previous molecular subtyping studies have defined four epidemic clones (ECs) of Listeria monocytogenes (ECI, ECII, ECIII, and ECIV). Partial sequences of eight virulence genes were previously shown to be identical within individual ECs of L. monocytogenes. The present study was conducted to determine if the sequences of other virulence genes and virulence gene regions are also conserved within these ECs. Six additional virulence genes—bsh, hly, inlJ, lplA1, pgdA, and srtA—and three additional virulence gene regions of actA, inlA, and inlB were selected based on their role in L. monocytogenes virulence, and intragenic regions of each gene were sequenced. Sequencing was performed on a diverse set of 44 to 48 L. monocytogenes strains. Results demonstrated that the sequenced regions of the nine virulence genes were identical within each of the ECs, and 257 new single nucleotide polymorphism (SNPs) were identified. ECIII (lineage II) was easily distinguishable from the other ECs, as 238 SNPs were observed in ECIII due to its significant evolutionary divergence from lineage I. With regard to the other ECs, there were 5 SNPs that represented an informative set, since these SNPs were able to differentiate specific ECs from all other unrelated strains used in this study. This study confirms our previous finding that virulence gene sequences are highly conserved within individual ECs and contain stable SNPs that can be used to very accurately differentiate ECs of L. monocytogenes from each other and from other diverse strains.

scholarly journals THE PROGNOSTIC SIGNIFICANCE OF TET2 SINGLE NUCLEOTIDE POLYMORPHISM IN EGYPTIAN CHRONIC MYELOID LEUKEMIA

2020 ◽  
Vol 12 (1) ◽  
pp. e2020004
Author(s):  
Enas A Dammag ◽  
Nahla A.M. Hamed ◽  
Nabil A El Halawani ◽  
Heba S Kassem ◽  
Mona W Ayad
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Statistical Significance ◽  
Control Group ◽  
Spleen Size ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Prognostic Criteria ◽  
And Control

Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. The pathogenesis of CML is based on the oncoprotein termed BCR‐ABL1. TET2 initiates DNA demethylation and is frequently mutated in hematological malignancies including CML.(1) The relation between TET2 acquisition and CML transformation and/or imitinab resistance is needed to be investigated. (2) Aim: To evaluate Ten Eleven Translocation 2 gene (TET2) single nucleotide polymorphism (SNP) (rs2454206, rs34402524, rs61744960) in chronic myeloid leukemia (CML) in relation to the disease prognostic criteria. Materials & Method: The study included 84 subjects; 54 CML in chronic phase and 30 healthy subjects as control group matched for age and sex. Routine investigations including CBC, bone marrow aspiration, biochemical investigations and molecular study were performed in CML patients to identify the disease stage. DNA extraction and SNP assay for TET2 gene polymorphism was done using (Thermo-Fisher predesigned SNP, USA) PCR prism 7500. Results: The mean age was 45.98±15.7 yrs in CML patients and   39.3±6.587 yrs in control group (p>0.05). TET2 SNP rs 34402524 was either heterozygous and homozygous in CML (48%,and 46.2%) but was mainly homozygous among control (80%) group (p=0.012). TET2 SNP rs 2454206 cases within CML (65.4%) and control (63.3%) group had wild patterns (p=0.046). TET2 SNP rs 61744960 showed a homozygous pattern among all groups (CML and control) showing no statistical significance (p=0.528). TET2 SNP in CML cases did not alter the prognostic criteria as no statistical significance was noted (p>0.05) yet, it was significantly related to spleen size in rs 34402524 where homozygous group had huger sizes and higher BCR-ABL1 levels 6 months after starting TKIs (p<0.05). Conclusions/Recommendation: TET2 SNP is a common in Egyptian chronic myeloid leukemia. TET2 SNP rs 3442524 was associated with huger spleen size and higher BCR-ABL1 levels after 6 months of starting TKIs suggesting disease progression.

scholarly journals Genome-Wide Association Study Meta-Analysis of Stroke in 22 000 Individuals of African Descent Identifies Novel Associations With Stroke

Stroke ◽  
2020 ◽  
Vol 51 (8) ◽  
pp. 2454-2463
Author(s):  
Keith L. Keene ◽  
Hyacinth I. Hyacinth ◽  
Joshua C. Bis ◽  
Steven J. Kittner ◽  
Braxton D. Mitchell ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Meta Analysis ◽  
African Descent ◽  
Genome Wide Association ◽  
Minority Population ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Genome Wide ◽  
A Genome

Background and Purpose: Stroke is a complex disease with multiple genetic and environmental risk factors. Blacks endure a nearly 2-fold greater risk of stroke and are 2× to 3× more likely to die from stroke than European Americans. Methods: The COMPASS (Consortium of Minority Population Genome-Wide Association Studies of Stroke) has conducted a genome-wide association meta-analysis of stroke in >22 000 individuals of African ancestry (3734 cases, 18 317 controls) from 13 cohorts. Results: In meta-analyses, we identified one single nucleotide polymorphism (rs55931441) near the HNF1A gene that reached genome-wide significance ( P =4.62×10 −8 ) and an additional 29 variants with suggestive evidence of association ( P <1×10 −6 ), representing 24 unique loci. For validation, a look-up analysis for a 100 kb region flanking the COMPASS single nucleotide polymorphism was performed in SiGN (Stroke Genetics Network) Europeans, SiGN Hispanics, and METASTROKE (Europeans). Using a stringent Bonferroni correction P value of 2.08×10 −3 (0.05/24 unique loci), we were able to validate associations at the HNF1A locus in both SiGN ( P =8.18×10 −4 ) and METASTROKE ( P =1.72×10 −3 ) European populations. Overall, 16 of 24 loci showed evidence for validation across multiple populations. Previous studies have reported associations between variants in the HNF1A gene and lipids, C-reactive protein, and risk of coronary artery disease and stroke. Suggestive associations with variants in the SFXN4 and TMEM108 genes represent potential novel ischemic stroke loci. Conclusions: These findings represent the most thorough investigation of genetic determinants of stroke in individuals of African descent, to date.

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