scholarly journals Interleukin 18 gene promoter polymorphisms in Latvian patients with rheumatoid arthritis

2011 ◽  
Vol 65 (1-2) ◽  
pp. 1-6
Author(s):  
Anna Mihailova ◽  
Helena Mikažāne ◽  
Jānis Kloviņs ◽  
Liene Ņikitina-Zaķe
Keyword(s):  
Rheumatoid Arthritis ◽  
Direct Sequencing ◽  
Gene Promoter ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Interleukin 18 ◽  
Promoter Polymorphisms ◽  
Phenotypic Data ◽  
Genome Database ◽  
American College Of Rheumatology

Interleukin 18 gene promoter polymorphisms in Latvian patients with rheumatoid arthritis Interleukin 18 (IL-18) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). There are controversial reports suggesting that IL-18 promoter polymorphisms may be an independent marker of RA susceptibility. The aim of the present study was to determine whether polymorphisms of the IL-18 gene promoter in positions -607 (rs 1946519) and -656 (rs 1946518) are associated with RA, and its characteristics in the Latvian population. We examined 105 patients with RA diagnosed according to the criteria of the American College of Rheumatology. DNA and phenotypic data from a healthy control population was obtained from Genome Database of Latvian Population. Genotypes were obtained by direct sequencing. Single-nucleotide polymorphisms (SNPs) were studied and frequencies of alleles and genotypes were compared between patients and controls. A P value less than 0.05 was accepted as statistically significant. There were no significant differences in the distribution of alleles and genotypes between RA patients and the control group. The frequencies of IL-18-607C/A and -656G/T genotypes differed between patients and the control group in women (P = 0.084 and 0.097). Heterozygous genotypes -607CA and -656GT occurred more frequently in the RA group than in the control (P = 0.046, P = 0.060), and this difference was also significant for the only women groups (P = 0.041,P = 0.054). The heterozygous states -607CA and -656GT of IL-18 gene affect susceptibility to RA. On the basis of investigated IL-18 polymorphisms, female patients with RA seem to represent a separate disease subgroup.

scholarly journals A Functional Haplotype of PADI4 Gene in Rheumatoid Arthritis: Positive Correlation in a French Population

2009 ◽  
Vol 36 (5) ◽  
pp. 881-886 ◽  
Author(s):  
FRÉDÉRIQUE GANDJBAKHCH ◽  
ISABELLE FAJARDY ◽  
BENJAMIN FERRÉ ◽  
SYLVAIN DUBUCQUOI ◽  
RENÉ-MARC FLIPO ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Direct Sequencing ◽  
Susceptibility Gene ◽  
Positive Association ◽  
Arginine Deiminase ◽  
Nucleotide Polymorphisms ◽  
Exon 2 ◽  
Asian Populations ◽  
American College Of Rheumatology ◽  
Elisa Technique

Objective.A functional haplotype of peptidyl arginine deiminase 4 (PADI4) was associated with susceptibility to rheumatoid arthritis (RA) in Asian populations, but the results are contradictory in Europeans. We investigated (1) the association of 2 single-nucleotide polymorphisms (SNP) located in exon 2 of PADI4 with RA in another Caucasian population; and (2) the association between PADI4 and anti-citrullinated protein (anti-CCP) antibodies.Methods.DNA samples were obtained from 405 French RA patients and 275 controls. All RA patients met the revised criteria of the American College of Rheumatology. PADI4_89 163(G→A) and PADI4_90 245(T→C) SNP were genotyped using a PCR-RFLP method confirmed by direct sequencing. All patients and controls were genotyped for HLA-DRB1. The presence of anti-CCP antibodies was tested in 243 RA patients using an ELISA technique.Results.We focused on PADI4_89 163(G→A) and PADI4_90 245(T→C) SNP that distinguished 2 main haplotypes: AC haplotype (PADI4_89*A PADI4_90*C) and GT haplotype (PADI4_89*G PADI4_90*T), described, respectively, as “nonsusceptible” and “susceptible.” A positive association between RA and presence of the GT haplotype was found in the heterozygous state (p = 0.002) and the homozygous state (RA patients 22%, controls 13%; p = 0.005). A correlation was observed between the presence but not the level of anti-CCP antibodies and the GT heterozygous (p = 0.03) and homozygous (p = 0.05) haplotypes. No correlation was found between the HLA-DRB1 shared epitope and any of the PADI4 haplotypes.Conclusion.Our findings confirm those of Japanese, Korean, and Canadian studies and suggest that PADI4 may be a new susceptibility gene independent of HLA-DRB1 for RA in Caucasian populations.

Abstract 631: Evaluation of Risk Factors for Cardiovascular Disease in Rheumatoid Arthritis

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Vitor M Rocha ◽  
Maria Guadalupe B Pippa
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Total Cholesterol ◽  
Normal Population ◽  
Control Group ◽  
American College Of Rheumatology ◽  
Increased Risk ◽  
Systemic Inflammatory Disease

Backgroung: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease, that appear to be responsible for 50% of mortality for thrombotic events such as Myocardial Infarction (MI) and Ischemic Stroke (SI) in RA patients. Occur approximately a decade earlier in these patients compared with the normal population. Objectives: To determine the risk of developing cardiovascular disease in patients with Rheumatoid Arthritis according to the classification criteria of the American College of Rheumatology. Methods: To assess the risk of cardiovascular diseases we studied 78 patients diagnosed with Rheumatoid Arthritis. For this we used the criteria of the risk score of Acute Coronary Disease in 10 years according to the Framingham Heart Study. A control group consisted of 21 patients with osteoarthritis and fibromyalgia was also assessed using the same criteria, where age, sex, systolic blood pressure values, total cholesterol, cholesterol HDL, presence of smoking and diagnosis of diabetes, were scored. Results: Patients with rheumatoid arthritis had a mean disease duration of 12.8 years (SD=7.4), age 58.6 years (SD=10.3) and the control group 59.3 years (SD=10,0). The old values of total cholesterol, HDL, blood pressure and being with Diabetes Mellitus showed positive correlations with the Cardiovascular Risk, and Blood Pressure in the index this correlation was stronger (r=+0.593) in Rheumatoid Arthritis and age (r=+0.702) in the control group. The Global Cardiovascular Risk in each group were considered low (7,8 points to Rematoid Artrhrits and 9,3 points to the control group). Conclusion: The results showed no increased risk of cardiovascular disease when compared to control group. Remember that control group fact be constituted by a larger number of diabetics, which likely impact these results.

scholarly journals Multiple Gene Polymorphisms Associated with Exfoliation Syndrome in the Uygur Population

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Nu Ma ◽  
Ting-Yu Xie ◽  
Xue-Yi Chen
Keyword(s):  
Protective Factor ◽  
Lysyl Oxidase ◽  
Direct Sequencing ◽  
Control Group ◽  
Exfoliation Syndrome ◽  
Nucleotide Polymorphisms ◽  
Age And Gender ◽  
Protective Allele ◽  
Significant Difference ◽  
And Gender

Background. Our previous data suggested that three single-nucleotide polymorphisms (SNPs), rs1048661, rs3825942, and rs2165241, of the lysyl oxidase-like 1 gene (LOXL1) are significantly associated with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). The following study investigated other SNPs that potentially effect XFS/XFG. Methods. A total of 216 Uygur patients diagnosed with XFS/XFG, and 297 Uygur volunteers were admitted to the First Affiliated Hospital at Xinjiang Medical University between January 2015 and October 2017. Blood samples were collected by venipuncture. Alleles and genotypes of LOXL1, TBC1D21, ATXN2, APOE, CLU, AFAP1, TXNRD2, CACNA1A, ABCA1, GAS7, and CNTNAP2 were analyzed by direct sequencing. Results. The allele G of rs41435250 of LOXL1 was a risk allele for XFS/XFG (P<0.001), whereas the allele G of rs893818 of LOXL1 was a protective allele for XFS/XFG (P<0.001). After adjusting all data for age and gender, the following results were obtained: the frequency of genotype CC for rs7137828 of ATXN2 was significantly higher in XFS/XFG patients than in controls (P=0.027), while no significance was found with reference to the frequency of genotype TT. The frequency of genotype GG for rs893818 of LOXL1 (P<0.001) and the frequency of genotype AA were both significantly higher in XFS/XFG groups compared to the control group (P<0.001). In addition, the frequency of genotype TT for rs41435250 of LOXL1 was higher in XFS/XFG patients than in controls (P=0.003), while no significant difference was found with reference to the frequency of genotype GG after adjusting for age and gender. In addition, the haplotypes G-A/T-G/G-G for rs41435250 and rs893818 were significantly associated with XFS/G. Conclusions. With reference to LOXL1, the rs41435250 resulted as a risk factor and rs893818 as a protective factor for XFS/XFG in the Uygur populations. Meanwhile, the rs16958445 of TBC1D21 and the rs7137828 of ATXN2 have also shown to be associated with pathogenesis of XFS/XFG.

scholarly journals Association Analysis of Single Nucleotide Polymorphisms in the 5′ Regulatory Region of the IL-6 Gene with Eimeria tenella Resistance in Jinghai Yellow Chickens

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 890 ◽  
Author(s):  
Hailiang Yu ◽  
Wenbin Zou ◽  
Shijie Xin ◽  
Xiaohui Wang ◽  
Changhao Mi ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Association Analysis ◽  
Direct Sequencing ◽  
Regulatory Region ◽  
Eimeria Tenella ◽  
Least Square ◽  
Bursa Of Fabricius ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Interleukin 6 (IL-6) is an immunoregulatory cytokine involved in various inflammatory and immune responses. To investigate the effects of single nucleotide polymorphisms (SNPs) and haplotypes of IL-6 on resistance to Eimeria tenella (E. tenella), SNPs in the 5′ regulatory region of IL-6 were detected with direct sequencing, and the effects of SNPs and haplotypes on resistance to E. tenella were analyzed by the least square model in Jinghai yellow chickens. Nineteen SNPs were identified in the 5′ regulation region of IL-6, among which three SNPs were newly discovered. The SNP association analysis results showed that nine of the SNPs were significantly associated with E. tenella resistance indexes; the A-483G locus was significantly associated with the GSH-Px, IL-2, and IL-17 indexes (p < 0.05); the C-447G locus was significantly associated with the SOD, GSH-Px, IL-17, and IL-2 indexes (p < 0.05); and the G-357A locus had significant effects on the CAT and IL-16 indexes (p < 0.05). Haplotype analysis showed that H2H3 and H2H5 were favorable haplotype combinations with good coccidium resistance. Furthermore, we used qRT-PCR and observed that the expression of IL-6 in the infection group was higher than that in the control group in the liver, proventriculus, small intestine, thymus, kidney, and bursa of Fabricius and extremely significantly different than that in the cecum especially (p < 0.01). In summary, SNPs and haplotypes in the 5′ regulatory region of IL-6 have important effects on E. tenella resistance, and the results will provide a reference for molecular marker selection of E. tenella resistance in Jinghai yellow chickens.

scholarly journals Identification of somatostatin receptor type 5 gene polymorphisms associated with acromegaly

2011 ◽  
Vol 165 (4) ◽  
pp. 517-525 ◽  
Author(s):  
Darja Ciganoka ◽  
Inga Balcere ◽  
Ivo Kapa ◽  
Raitis Peculis ◽  
Andra Valtere ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Somatostatin Receptor ◽  
Strong Association ◽  
Upstream Region ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Additional Group ◽  
Unstandardized Regression Coefficient ◽  
Design And Methods

ObjectiveThe aim of this study was to characterize the genetic variance of somatostatin receptor 5 (SSTR5) and investigate the possible correlation of such variants with acromegaly risk and different disease characteristics.Design and methodsThe SSTR5 gene coding region and 2000 bp upstream region was sequenced in 48 patients with acromegaly and 96 control subjects. Further, three single nucleotide polymorphisms (SNPs) were analyzed in the same group of acromegaly patients and in an additional group of 475 age- and sex-matched controls.ResultsIn total, 19 SNPs were identified in the SSTR5 gene locus by direct sequencing. Three SNPs (rs34037914, rs169068, and rs642249) were significantly associated with the presence of acromegaly using the initial controls. The allele frequencies were significantly (P<0.01) different between the acromegaly patients and the additional large control group. rs34037914 and rs642249 remained significantly associated with acromegaly after Bonferroni correction and permutation tests (odds ratio (OR)=3.38; 95% confidence interval (CI), 1.78–6.42; P=0.00016 and OR=2.41; 95% CI, 1.41–4.13; P=0.0014 respectively). Haplotype reconstruction revealed two possible risk haplotypes determined by rs34037914 (633T) and rs642249 (1044A) alleles. Both haplotypes were found in significantly higher frequency in acromegaly patients compared with controls (P<0.001). In addition, the 663T allele was significantly associated with a younger age of acromegaly diagnosis (unstandardized regression coefficient β=−10.4; P=0.002), increased body mass index (β=4.1; P=0.004), higher number of adenoma resection (P<0.001) and lack of observable tumor shrinkage after somatostatin analog treatment (P=0.014).ConclusionsOur results demonstrate a previously undetected strong association of two SSTR5 SNPs with acromegaly. The data also suggest a possible involvement of SSTR5 variants in decreased suppression of GH production and increased tumor proliferation.

scholarly journals Disease association of two distinct interleukin-18 promoter polymorphisms in Caucasian rheumatoid arthritis patients

2005 ◽  
Vol 6 (3) ◽  
pp. 211-216 ◽  
Author(s):  
J A Gracie ◽  
N Koyama ◽  
J Murdoch ◽  
M Field ◽  
F McGarry ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Association ◽  
Interleukin 18 ◽  
Promoter Polymorphisms

scholarly journals Genetic Polymorphisms in Cytokine Genes in Colombian Patients with Ocular Toxoplasmosis

2018 ◽  
Vol 86 (4) ◽  
pp. e00597-17 ◽  
Author(s):  
C. A. Naranjo-Galvis ◽  
A. de-la-Torre ◽  
L. E. Mantilla-Muriel ◽  
L. Beltrán-Angarita ◽  
X. Elcoroaristizabal-Martín ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Gene Promoter ◽  
Protozoan Parasite ◽  
Ocular Toxoplasmosis ◽  
Nucleotide Polymorphisms ◽  
Promoter Polymorphisms ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Cytokine Genes ◽  
Ifn Γ

ABSTRACT Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii, which has the capacity to infect all warm-blooded animals worldwide. Toxoplasmosis is a major cause of visual defects in the Colombian population; however, the association between genetic polymorphisms in cytokine genes and susceptibility to ocular toxoplasmosis has not been studied in this population. This work evaluates the associations between polymorphisms in genes coding for the cytokines tumor necrosis factor alpha (TNF-α) (rs1799964, rs1800629, rs1799724, rs1800630, and rs361525), interleukin 1β (IL-1β) (rs16944, rs1143634, and rs1143627), IL-1α (rs1800587), gamma interferon (IFN-γ) (rs2430561), and IL-10 (rs1800896 and rs1800871) and the presence of ocular toxoplasmosis (OT) in a sample of a Colombian population (61 patients with OT and 116 healthy controls). Genotyping was performed with the “dideoxynucleotide (ddNTP) primer extension” technique. Functional-effect predictions of single nucleotide polymorphisms (SNPs) were done by using FuncPred. A polymorphism in the IL-10 gene promoter (−1082G/A) was significantly more prevalent in OT patients than in controls (P = 1.93e−08; odds ratio [OR] = 5.27e+03; 95% confidence interval [CI] = 3.18 to 8.739; Bonferroni correction [BONF] = 3.48e−07). In contrast, haplotype “AG” of the IL-10 gene promoter polymorphisms (rs1800896 and rs1800871) was present at a lower frequency in OT patients (P = 7e−04; OR = 0.10; 95% CI = 0.03 to 0.35). The +874A/T polymorphism of IFN-γ was associated with OT (P = 3.37e−05; OR = 4.2; 95% CI = 2.478 to 7.12; BONF = 6.07e−04). Haplotype “GAG” of the IL-1β gene promoter polymorphisms (rs1143634, rs1143627, and rs16944) appeared to be significantly associated with OT (P = 0.0494). The IL-10, IFN-γ, and IL-1β polymorphisms influence the development of OT in the Colombian population.

scholarly journals Incorporating adjustments for variability in control group response rates in network meta-analysis: a case study of biologics for rheumatoid arthritis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chris Cameron ◽  
Abhishek Varu ◽  
Arthur Lau ◽  
Mahdi Gharaibeh ◽  
Marcelo Paulino ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Meta Analysis ◽  
Response Rates ◽  
Control Group ◽  
Severe Rheumatoid Arthritis ◽  
American College Of Rheumatology ◽  
Group Response ◽  
Study Heterogeneity ◽  
Treatment Comparisons

Abstract Background The importance of adjusting for cross-study heterogeneity in control group response rates when conducting network meta-analyses (NMA) was demonstrated using a case study involving a comparison of biologics for the treatment of moderate-to-severe rheumatoid arthritis. Methods Bayesian NMAs were conducted for American College of Rheumatology (ACR) 50 treatment response based upon a set of randomized controlled trials (RCTs) identified by a recently completed systematic review of the literature. In addition to the performance of an unadjusted NMA, a model adjusting for cross-study heterogeneity of control group response rates using meta-regression was fit to the data. Model fit was evaluated, and findings from both analyses were compared with regard to clinical interpretations. Results ACR 50 response data from a total of 51 RCTs and 16,223 patients were analyzed. Inspection of cross-study variability in control group response rates identified considerable differences between studies. NMA incorporating adjustment for this variability was associated with an average change of 38.1% in the magnitude of the ORs between treatment comparisons, and over 64% of the odds ratio changed by 15% or more. Important changes in the clinical interpretations drawn from treatment comparisons were identified with this improved modeling approach. Conclusions In comparing biologics for moderate to severe rheumatoid arthritis, failure to adjust for cross-trial differences in the control arm response rates in NMA can lead to biased estimates of comparative efficacy between treatments.

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