scholarly journals PADI4 Polymorphisms Confer Risk of Anti-CCP-Positive Rheumatoid Arthritis in Synergy With HLA-DRB1*04 and Smoking

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Massarenti ◽  
Christian Enevold ◽  
Dres Damgaard ◽  
Niels Ødum ◽  
Peter Garred ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Smoking Status ◽  
Nucleotide Polymorphisms ◽  
Regression Analyses ◽  
Post Translational Modification ◽  
Pathogenic Role ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Citrullinated Protein ◽  
Reduced Risk

Peptidylarginine deiminases (PADs) catalyze citrullination, a post-translational modification playing a pathogenic role in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA). The interplay between single nucleotide polymorphisms (SNPs) in the PADI genes and known risk factors for ACPA-positive RA, including smoking, HLA-DR4 and -1, and the PTPN22 R620W polymorphism, was investigated. We typed four PADI2 SNPs, four PADI4 SNPs, and the PTPN22 R620W SNP in 445 Danish RA patients and 533 age-matched healthy controls, as well as in 200 North American RA patients and 100 age- and sex-matched controls. The HLA-DRB1 locus was typed in the Danish cohort. Logistic regression analyses, adjusted for age, sex, smoking status, and PTPN22 R620W, revealed increased risk of anti-CCP-positive RA in carriers of rs11203367(T) (OR: 1.22, p=0.03) and reduced risk in carriers of rs2240335(A) in PADI4 (OR: 0.82, p=0.04). rs74058715(T) in PADI4 conferred reduced risk of anti-CCP-negative RA (OR: 0.38, p=0.003). In HLA-DRB1*04-positive individuals, specifically, the risk of anti-CCP-positive RA was increased by carriage of PADI4 rs1748033(T) (OR: 1.54, p=0.007) and decreased by carriage of PADI4 rs74058715(T) (OR: 0.44, p=0.01), and we observed an interaction between these SNPs and HLA-DRB1*04 (p=0.004 and p=0.008, respectively) Thus, PADI4 polymorphisms associate with ACPA-positive RA, particularly in HLA-DRB1*04-positive individuals, and with ACPA-negative RA independently of HLA-DRB1*04.

Susceptible genes of restless legs syndrome in migraine

Cephalalgia ◽  
2016 ◽  
Vol 36 (11) ◽  
pp. 1028-1037 ◽  
Author(s):  
Jong-Ling Fuh ◽  
Ming-Yi Chung ◽  
Shu-Chih Yao ◽  
Ping-Kun Chen ◽  
Yi-Chu Liao ◽  
...  
Keyword(s):  
Restless Legs Syndrome ◽  
Genetic Variants ◽  
Multivariate Regression ◽  
Iron Homeostasis ◽  
Nucleotide Polymorphisms ◽  
Regression Analyses ◽  
Single Nucleotide ◽  
Association Analyses ◽  
Restless Legs ◽  
Increased Risk

Objective Several genetic variants have been found to increase the risk of restless legs syndrome (RLS). The aim of the present study was to determine if these genetic variants were also associated with the comorbidity of RLS and migraine in patients. Methods Thirteen single-nucleotide polymorphisms (SNPs) at six RLS risk loci ( MEIS1, BTBD9, MAP2K5, PTPRD, TOX3, and an intergenic region on chromosome 2p14) were genotyped in 211 migraine patients with RLS and 781 migraine patients without RLS. Association analyses were performed for the overall cohort, as well as for the subgroups of patients who experienced migraines with and without aura and episodic migraines (EMs) vs. chronic migraines (CMs). In order to verify which genetic markers were potentially related to the incidence of RLS in migraine patients, multivariate regression analyses were also performed. Results Among the six tested loci, only MEIS1 was significantly associated with RLS. The most significant SNP of MEIS1, rs2300478, increased the risk of RLS by 1.42-fold in the overall cohort ( p = 0.0047). In the subgroup analyses, MEIS1 augmented the risk of RLS only in the patients who experienced EMs (odds ratio (OR) = 1.99, p = 0.0004) and not those experiencing CMs. Multivariate regression analyses further showed that rs2300478 in MEIS1 (OR = 1.39, p = 0.018), a CM diagnosis (OR = 1.52, p = 0.022), and depression (OR = 1.86, p = 0.005) were independent predictors of RLS in migraine. Conclusions MEIS1 variants were associated with an increased risk of RLS in migraine patients. It is possible that an imbalance in iron homeostasis and the dopaminergic system may represent a link between RLS incidence and migraines.

PADI4 polymorphism predisposes male smokers to rheumatoid arthritis

2010 ◽  
Vol 70 (3) ◽  
pp. 512-515 ◽  
Author(s):  
Yuta Kochi ◽  
Mohamed M Thabet ◽  
Akari Suzuki ◽  
Yukinori Okada ◽  
Nina A Daha ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Smoking Status ◽  
Arginine Deiminase ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Logistic Regression Models ◽  
Environmental Interactions ◽  
Never Smokers ◽  
European Populations

ObjectiveTo elucidate the differential role of peptidyl arginine deiminase 4 (PADI4) polymorphism in rheumatoid arthritis (RA) between Asian and European populations, possible gene–environmental interactions among the PADI4 polymorphism, sex and smoking status were analysed.MethodsThree independent sets of case–control samples were genotyped for single-nucleotide polymorphisms in PADI4; Japanese samples (first set, 1019 RA patients, 907 controls; second set, 999 RA patients, 1128 controls) using TaqMan assays and Dutch samples (635 RA patients, 391 controls) using Sequenom MassARRAY platform. The association of PADI4 with RA susceptibility was evaluated by smoking status and sex in contingency tables and logistic regression models.ResultsIn the first set of Japanese samples, PADI4 polymorphism (rs1748033) showed a greater risk in men (ORallele 1.39; 95% CI 1.10 to 1.76; ptrend=0.0054) than in women and in ever-smokers (ORallele 1.25; 95% CI 1.02 to 1.53; ptrend=0.032) than in never-smokers. Moreover, the highest risk was seen in male ever-smokers (ORallele 1.46; 95% CI 1.12 to 1.90; ptrend=0.0047). Similar trends were observed in the second set of Japanese samples as well as in Dutch samples.ConclusionPADI4 polymorphism highly predisposes male smokers to RA, and the genetic heterogeneity observed between Asian and European populations may be partly explained by differences in smoking prevalence among men.

HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBV+ Hodgkin lymphoma

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3310-3315 ◽  
Author(s):  
Marijke Niens ◽  
Ruth F. Jarrett ◽  
Bouke Hepkema ◽  
Ilja M. Nolte ◽  
Arjan Diepstra ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Hla Class I ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Barr Virus ◽  
Increased Risk ◽  
Peptide Binding Groove ◽  
Epstein Barr ◽  
Binding Groove ◽  
Reduced Risk

AbstractPrevious studies showed that the HLA class I region is associated with Epstein-Barr virus (EBV)–positive Hodgkin lymphoma (HL) and that HLA-A is the most likely candidate gene in this region. This suggests that antigenic presentation of EBV-derived peptides in the context of HLA-A is involved in the pathogenesis of EBV+ HL by precluding efficient immune responses. We genotyped exons 2 and 3, encoding the peptide-binding groove of HLA-A, for 32 single nucleotide polymorphisms in 70 patients with EBV+ HL, 31 patients with EBV− HL, and 59 control participants. HLA-A*01 was significantly overrepresented and HLA-A*02 was significantly underrepresented in patients with EBV+ HL versus controls and patients with EBV− HL. In addition, HLA-A*02 status was determined by immunohistochemistry or HLA-A*02–specific polymerase chain reaction (PCR) on 152 patients with EBV+ HL and 322 patients with EBV− HL. The percentage of HLA-A*02+ patients in the EBV+ HL group (35.5%) was significantly lower than in 6107 general control participants (53.0%) and the EBV− HL group (50.9%). Our results indicate that individuals carrying the HLA-A*02 allele have a reduced risk of developing EBV+ HL, while individuals carrying the HLA-A*01 allele have an increased risk. It is known that HLA-A*02 can present EBV-derived peptides and can evoke an effective immune response, which may explain the protective phenotype.

A single nucleotide polymorphism in the IRF5 promoter region is associated with susceptibility to rheumatoid arthritis in the Japanese population

2008 ◽  
Vol 68 (3) ◽  
pp. 377-383 ◽  
Author(s):  
K Shimane ◽  
Y Kochi ◽  
R Yamada ◽  
Y Okada ◽  
A Suzuki ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Human Leukocyte ◽  
Promoter Polymorphism ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Leukocyte Antigen ◽  
Asian Populations ◽  
Increased Risk ◽  
Stratified Analysis ◽  
Japanese Subjects

Objectives:Interferon regulatory factor 5 (IRF5) is a member of the IRF family of transcription factors, which regulate the production of proinflammatory cytokines. Polymorphisms in the IRF5 gene have been associated with susceptibility to systemic lupus erythaematosus (SLE) in Caucasian and Asian populations, but their involvement in other autoimmune diseases is still uncertain. Here, we assessed the genetic role of IRF5 in susceptibility to rheumatoid arthritis (RA) in Japanese subjects.Methods:We selected 13 single nucleotide polymorphisms (SNPs) and a CGGGG insertion–deletion polymorphism in the IRF5 gene. We performed 2 sets of case–control comparisons using Japanese subjects (first set: 830 patients with RA and 658 controls; second set: 1112 patients with RA and 940 controls), and then performed a stratified analysis using human leukocyte antigen (HLA)-DRB1 shared epitope (SE) status. We genotyped the SNPs using TaqMan assays.Results:A significant association of the rs729302 A allele with RA susceptibility was found in both sets (odds ratio (OR) 1.22, 95% CI 1.09 to 1.35, p<0.001 in the combined analysis). When the patients were stratified by the SE, the rs729302 A allele was found to confer increased risk to RA in patients that were SE negative (OR 1.50, 95% CI 1.17 to 1.92, p = 0.001) as compared with patients carrying the SE (OR 1.11, 95% CI 0.93 to 1.33, p = 0.24). In both sets, no genotyped polymorphisms were significantly associated with RA susceptibility, but rs729302 was significantly associated.Conclusions:These findings indicate that the promoter polymorphism of IRF5 is a genetic factor conferring predisposition to RA, and that it contributes considerably to disease pathogenesis in patients that were SE negative.

scholarly journals Genetic Factors Associated with COPD Depend on the Ancestral Caucasian/Amerindian Component in the Mexican Population

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 599
Author(s):  
Gloria Pérez-Rubio ◽  
Ramcés Falfán-Valencia ◽  
Juan Carlos Fernández-López ◽  
Alejandra Ramírez-Venegas ◽  
Rafael de Jesús Hernández-Zenteno ◽  
...  
Keyword(s):  
Lower Risk ◽  
Genetic Factors ◽  
Principal Component ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genotyping Array ◽  
Mexican Mestizo ◽  
Factors Associated ◽  
Increased Risk ◽  
Reduced Risk

Genetic variability influences the susceptibility to and severity of complex diseases; there is a lower risk of COPD in Hispanics than in non-Hispanic Caucasians. In this study, we included 830 Mexican-Mestizo subjects; 299 were patients with COPD secondary to tobacco smoking, and 531 were smokers without COPD. We employed a customized genotyping array of single nucleotide polymorphisms (SNPs). The population structure was evaluated by principal component analysis and allele association through a logistic regression model and haplotype identification. In this study, 118 individuals were identified with a high Caucasian component and 712 with a high Amerindian component. Independent of the ancestral contribution, two SNPs were associated with a reduced risk (p ≤ 0.01) of developing COPD in the CYP2A6 (rs4105144) and CYP2B6 (rs10426235) genes; however, a haplotype was associated with an increased risk of COPD (p = 0.007, OR = 2.47) in the CHRNA5-CHRNA3 loci among smokers with a high Caucasian component. In Mexican-Mestizo smokers, there are SNPs in genes that encode proteins responsible for the metabolism of nicotine associated with a lower risk of COPD; individuals with a high Caucasian component harboring a haplotype in the CHRNA5-CHRNA3 loci have a higher risk of suffering from COPD.

scholarly journals G-1639A but Not C1173TVKORC1Gene Polymorphism Is Related to Ischemic Stroke and Its Various Risk Factors in Ukrainian Population

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Yevhen I. Dubovyk ◽  
Viktoriia Yu. Harbuzova ◽  
Alexander V. Ataman
Keyword(s):  
Ischemic Stroke ◽  
Vitamin K ◽  
Protective Factor ◽  
Smoking Status ◽  
Transmembrane Protein ◽  
Polymorphism Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Pcr Rflp

Vitamin K epoxide reductase complex subunit 1 (VKORC1) is integral 163-amino acid long transmembrane protein which mediates recycling of vitamin K 2,3-epoxide to vitamin K hydroquinone and it is necessary for activation of vitamin K-dependent proteins (VKDPs). Herein, the association between G-1639A (rs9923231) and C1173T (rs9934438) single-nucleotide polymorphisms (SNPs) of theVKORC1gene and ischemic stroke (IS) was tested in Ukrainian population. Genotyping was performed in 170 IS patients and 124 control subjects (total 294 DNA samples) using PCR-RFLP (polymerase chain reaction with following restriction fragment length polymorphism analysis) method. Our data showed that G-1639A but not C1173T polymorphism was related to IS, regardless of adjustment for age, sex, body mass index, smoking status, and arterial hypertension. The risk for IS in -1639A allele carriers (OR = 2.138,P=0.015) was higher than in individuals with G/G genotype. Haplotype analysis demonstrated that -1639G/1173T and -1639A/1173C were related to increased risk for IS (OR = 3.813,P=0.010,and OR = 2.189,P=0.011, resp.), while -1639G/1173C was a protective factor for IS (OR = 0.548,P<0.001). Obtained results suggested that -1639A allele can be a possible genetic risk factor for IS in Ukrainian population.

scholarly journals HLA-DRB1*07:01 and *08:02 Alleles Confer a Protective Effect Against ACPA-Positive Rheumatoid Arthritis in a Latin American Admixed Population

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 467
Author(s):  
Patricia Castro-Santos ◽  
Jordi Olloquequi ◽  
Ricardo A. Verdugo ◽  
Miguel A. Gutiérrez ◽  
Carmen Pinochet ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Latin American ◽  
Protective Effects ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Histocompatibility Complex ◽  
Disease Associations ◽  
Admixed Population ◽  
First Time ◽  
Citrullinated Protein

HLA-DRB1 shared epitope (SE) alleles are important genetic contributors for the risk of developing anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis (RA), particularly in Caucasians. We aimed to analyze the contribution of HLA-DRB1 alleles and single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC) region to the susceptibility to develop ACPA-positive RA in a Latin American (LA) population with admixed ancestry. A total of 289 ACPA-positive RA patients and 510 controls were enrolled in this study. The presence of HLA-DRB1*04:01, *09:01 and *10:01 was increased in ACPA-positive RA patients compared with healthy controls (p < 0.0001, p < 0.001 and p < 0.01, respectively), whereas DRB1*07:01 and *08:02 was associated with a decreased risk of ACPA-positive RA (p < 0.001 and p < 0.01, respectively). These results showed a strong correlation with estimates from studies in Asians but not in Caucasian populations. The present study describes the protective effects of the HLA-DRB1*07:01 and *08:02 alleles in ACPA-positive RA patients in a LA population for the first time. Identifying relationships between HLA-DRB1 alleles and RA is important for identifying disease associations in different ethnic groups in order to reach a better understanding of RA worldwide.

scholarly journals SERPINA1 and HSD17B13 Gene Variants in Patients with Liver Fibrosis and Cirrhosis

2019 ◽  
Vol 28 (3) ◽  
pp. 297-302 ◽  
Author(s):  
Viktorija Basyte-Bacevice ◽  
Jurgita Skieceviciene ◽  
Irena Valantiene ◽  
Jolanta Sumskiene ◽  
Vitalija Petrenkiene ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Cirrhosis ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
P Value ◽  
Gene Variants ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Reduced Risk

Background & Aims: Two single nucleotide polymorphisms (SNPs) in SERPINA1 (Pi*Z rs28929474 and Pi*Srs17580) are risk factors for developing liver cirrhosis. A recent study identified a common SNP in HSD17B13(rs72613567) that conferred protection from chronic liver disease. The aim of the present study was to testthese associations in a cohort of Lithuanian patients with liver fibrosis or cirrhosis. Methods: The study included 302 patients with cirrhosis, 127 patients with liver fibrosis (METAVIR stagesI-III) and 548 controls, all from Lithuania. SNPs were genotyped by quantitative PCR, using TaqMan allelicdiscrimination assays. Adjusted p value of ≤ 0.016 was considered significant. Results: Genotype distributions of SERPINA1 and HSD17B13 SNPs were in Hardy-Weinberg equilibrium.SERPINA1 Pi*Z was not associated with liver fibrosis or cirrhosis. HSD17B13 rs10433937 (in high linkagedisequilibrium with rs72613567; r 2 =0.96) also showed no overall association with liver disease, but the GG-genotype was associated with reduced risk of liver fibrosis (aOR 0.37, p=0.03). SERPINA1 Pi*S was associatedwith higher risk of developing hepatic fibrosis (aOR 3.42, p=0.001) and cirrhosis (aOR 2.59, p=0.02). Conclusions: We found that SERPINA1 Pi*S variant conferred an increased risk of developing liver fibrosis,while SERPINA1 Pi*Z and HSD17B13 rs10433937 were not associated with liver fibrosis or cirrhosis ofdifferent aetiology.

scholarly journals Association of rs3135500 and rs3135499 Polymorphisms in the MicroRNAbinding Site of Nucleotide-binding Oligomerization Domain 2 (NOD2) Gene with Susceptibility to Rheumatoid Arthritis

2021 ◽  
Author(s):  
Naeim Ehtesham ◽  
Behrang Alani ◽  
Deniz Mortazavi ◽  
Sara Azhdari ◽  
Taiebe Kenarangi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Responses ◽  
Nucleotide Binding ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Reactive Protein ◽  
Increased Risk ◽  
First Time ◽  
Control Study ◽  
Oligomerization Domain

The nucleotide-binding oligomerization domain 2 (NOD2) is the key regulator of inflammatory responses and has been involved in the pathogenesis of rheumatoid arthritis (RA). Laboratory and in silico evaluations have demonstrated that some polymorphisms in 3ˊUTR of NOD2 gene could influence the secondary structure of this region and similarly thermodynamic features of hybridization site and finally deregulate the expression of NOD2. In the current study, for the first time, we evaluated the possible association between single nucleotide polymorphisms (SNPs) rs3135500 and rs3135499 in the NOD2 gene with RA risk in the Iranian population. One hundred and fifteen patients with RA and 120 healthy subjects were recruited in this case-control study. Genotyping of rs3135500 and rs3135499 polymorphisms were accomplished using the real‑time polymerase chain reaction high resolution melting (HRM) method. We found a substantial association of AA and AG genotypes in rs3135500 with the risk of RA (AA vs GG; OR=5.547; 95%CI [2.564-11.999]; p<0.001 and AG vs GG; OR=2.179; 95%CI [1.145-4.147]; p=0.017). Moreover, in the patient group, there was a significant relationship between the increased concentration of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with rs3135500 (A allele) (p<0.05). However, there were no important associations between rs3135499 with the risk of RA (p>0.05). However, we found a noteworthy association of the C allele in rs3135499 with an increased level of CRP in patients (p>0.05). Our findings propose a considerable association between NOD2 polymorphisms with increased risk of RA and disease activity.

scholarly journals Associations of polymorphic variants of the vascular endothelial growth factor А gene with the development of coronary heart disease in Central Russia

2020 ◽  
pp. 52-53
Author(s):  
М.В. Медведева ◽  
М.А. Солодилова ◽  
М.А. Быканова ◽  
Н.В. Иванова ◽  
А.В. Полоников
Keyword(s):  
Vascular Endothelial ◽  
Nucleotide Polymorphisms ◽  
Vegf Gene ◽  
Single Nucleotide ◽  
Central Russia ◽  
Increased Risk ◽  
Polymorphic Variants ◽  
Negative Coupling ◽  
Endothelial Growth Factor ◽  
Reduced Risk

Изучен вклад однонуклеотидных полиморфизмов (SNPs) rs3025039, rs833061, rs3025000 и rs833068 гена VEGFA в развитие ишемической болезни сердца (ИБС). Установлена ассоциация rs3025039, rs833061 и rs3025000 с ИБС у мужчин. При изучении гаплотипов установлены ассоциации rs833061T-rs833068A-rs3025000T-rs3025039C и rs833061T-rs833068G-rs3025000C- rs3025039С с пониженным риском развития ИБС у мужчин, гаплотипа rs833061C-rs833068G-rs3025000C-rs3025039T и редких гаплотипов (частота <1%) - с повышенным риском развития ИБС у женщин. Также в работе было выявлено, что аллель rs833061T находится в отрицательном неравновесии по сцеплению (LD) с аллелями rs833068G и rs3025000C у мужчин и положительном LD у женщин, а rs3025039 - в слабом положительном LD с SNP rs3025039 у мужчин. The contribution of single-nucleotide polymorphisms (SNPs) rs3025039, rs833061, rs3025000 and rs833068 of the VEGF gene to the development of CHD was studied. The Association of rs3025039, rs833061 and rs3025000 with CHD in men was established. The study of haplotypes established associations rs833061T-rs833068A-rs3025000T-rs3025039C and rs833061T-rs833068G-rs3025000C - gs3025039c with a reduced risk of CHD in men, haplotype rs833061C-rs833068G-rs3025000C-rs3025039T and rare haplotypes (frequency <1%) - with an increased risk of CHD in men CHD in women. It was also found that the rs833061T allele is in a negative coupling disequilibrium (LD) with the rs833068G and rs3025000C alleles in men and a positive LD in women, and rs3025039 is in a weak positive LD with the SNP rs3025039 in men.

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