KDR (VEGFR2) Genetic Variants and Serum Levels in Patients with Rheumatoid Arthritis

We investigated kinase insert domain-containing receptor (KDR) polymorphisms and protein levels in relation to susceptibility to and severity of Rheumatoid Arthritis (RA). 641 RA patients and 340 controls (HC) were examined for the rs1870377 KDR variant by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method and for rs2305948 and rs2071559 KDR single nucleotide polymorphisms (SNPs) by TaqMan SNP genotyping assay. KDR serum levels were determined by enzyme-linked immunosorbent assay (ELISA). The rs1870377 KDR variant has shown association with RA under the codominant (p = 0.02, OR = 1.76, 95% CI = 1.09–2.85) and recessive models (p = 0.019, OR = 1.53, 95% CI = 1.07–2.20). KDR rs2305948 was associated with RA under the dominant model (p = 0.005, OR = 1.38, 95% CI = 1.10–1.73). Under the codominant model, the frequency of the rs2071559 TC and GG genotypes were lower in RA patients than in controls (p < 0.001, OR = 0.51, 95% CI = 0.37–0.69, and p = 0.002, OR = 0.57, 95% CI = 0.39–0.81). KDR rs2071559 T and rs2305948 A alleles were associated with RA (p = 0.001, OR = 0.60, 95% CI = 0.45–0.81 and p = 0.008, OR = 1.71, CI = 1.15–2.54). KDR rs2305948SNP was associated with Disease Activity Score (DAS)-28 score (p < 0.001), Visual Analog Scale (VAS) score (p < 0.001), number of swollen joints (p < 0.001), mean value of CRP (p < 0.001). A higher KDR serum level was found in RA patients than in HC (8018 pg/mL versus 7381 pg/mL, p = 0.002). Present results shed light on the role of KDR genetic variants in the severity of RA.

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Association of the Adipokines Chemerin, Apelin, Vaspin and Omentin and Their Functional Genetic Variants with Rheumatoid Arthritis

Journal of Personalized Medicine ◽

10.3390/jpm11100976 ◽

2021 ◽

Vol 11 (10) ◽

pp. 976

Author(s):

Alaa S. Wahba ◽

Maha E. Ibrahim ◽

Dina M. Abo-elmatty ◽

Eman T. Mehanna

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Genetic Variants ◽

Serum Levels ◽

Expression Levels ◽

Protein Levels ◽

Egyptian Patients ◽

Gene Expression Levels ◽

Increased Susceptibility

Adipokines were shown to exert crucial roles in rheumatic diseases. This study aimed to assess the role of chemerin, apelin, vaspin, and omentin adipokines and their genetic variants rs17173608, rs2235306, rs2236242, and rs2274907, respectively, in rheumatoid arthritis (RA) pathogenesis in Egyptian patients. A total of 150 RA patients and 150 healthy individuals were recruited. Blood samples were collected and used for genotyping. Serum was separated and used for expression analysis by quantitative PCR, and various biochemical markers determination by ELISA. Serum protein levels of chemerin and vaspin, as well as their gene expression levels were higher, while those of apelin and omentin were lower in RA patients and were associated with most of RA clinical and laboratory characteristics. G allele of chemerin rs17173608, T allele of vaspin rs2236242, and T allele of omentin rs2274907 were more frequent in RA patients. Serum levels and gene expression levels of chemerin in GG genotype carriers and vaspin in TT genotype group were significantly higher, while those of omentin in TT genotype carriers were significantly lower than RA patients with other genotypes. There was no association between apelin rs2235306 and RA. Chemerin rs17173608, vaspin rs2236242, and omentin rs2274907 polymorphisms were associated with increased susceptibility to RA.

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Plasma interleukin-21 levels and genetic variants are associated with susceptibility to rheumatoid arthritis

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-04111-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Youguo Hao ◽

Lijun Xie ◽

Jing Xia ◽

Zhen Liu ◽

Baoxiu Yang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Genetic Variants ◽

Chinese Population ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Das28 Score ◽

Single Nucleotide ◽

Chronic Inflammatory Condition ◽

Chinese Subjects ◽

Pro Inflammatory Cytokines

Abstract Background Rheumatoid Arthritis (RA) is a chronic inflammatory condition characterized by autoantibodies development and an elevated spectrum of pro-inflammatory cytokines. Previous reports highlighted a relationship between IL-21and the pathogenesis of RA. Although elevated IL-21 levels have been reported in RA patients, the association of common IL-21 genetic variants with a predisposition to RA development in the Chinese population lacks. Materials and methods Five hundred and fourteen Chinese subjects (healthy controls: 303 and rheumatoid arthritis patients: 211) were enrolled in the study. Clinical data of patients were collected from medical records, and patients were treated as per the guidelines. Common single nucleotide polymorphisms in the IL-21 gene (rs907715, rs2221903, rs2055979 and rs6822844) were genotyped by TaqMan SNPs genotyping method. IL-21 level in plasma of RA patients and healthy subjects was measured by ELISA. Results The plasma level of IL-21 was significantly higher in subjects with rheumatoid arthritis relative to healthy controls (p < 0.0001). A positive correlation was observed between IL-21 level and DAS28 score, indicating the association of the cytokine with the worsening of the disease (Spearman r = 0.61, p < 0.0001). The prevalence of AA genotype (rs2055979) was significantly higher in RA subjects than in the controls (p < 0.0001, χ2 = 34.73, OR = 4.34, 95% CI = 2.623 to 7.219). Furthermore, elevated plasma IL-21 was observed in the rs2055979-AA genotype compared to CC type (p < 0.0001). Conclusion IL-21 plays a crucial function in rheumatoid arthritis pathogenesis. IL-21 rs2055979 polymorphism is associated with IL-21 plasma levels and is predisposed to RA development in the Chinese population.

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PADI4 polymorphism predisposes male smokers to rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/ard.2010.130526 ◽

2010 ◽

Vol 70 (3) ◽

pp. 512-515 ◽

Cited By ~ 38

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.

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SNP rs2073618 of the Osteoprotegerin Gene Is Associated with Diabetic Retinopathy in Slovenian Patients with Type 2 Diabetes

BioMed Research International ◽

10.1155/2013/364073 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Sara Mankoč Ramuš ◽

Tina Kumše ◽

Mojca Globočnik Petrovič ◽

Daniel Petrovič ◽

Ines Cilenšek

Keyword(s):

Type 2 Diabetes ◽

Diabetic Retinopathy ◽

Strong Association ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Regulatory Molecule ◽

Codominant Model ◽

Osteoprotegerin Gene

Recent studies indicate that osteoprotegerin (OPG) acts as an important regulatory molecule in the vasculature. Also, a strong association was observed between circulation OPG and microvascular complication. By considering the possible role of OPG in diabetic retinopathy (DR) we examined two of the most studied polymorphisms of the OPG genes rs2073618 (located in exon I) and rs3134069 (located in the promoter region) and their relation to DR in Slovenian patients with type 2 diabetes. Logistic regression analysis demonstrated that the carriers of the CC genotype had a 2.2 higher risk for DR than those with either the CG genotype or the GG genotype (codominant model for rs2073618). Furthermore, the combined effect of single nucleotide polymorphisms (SNPs) rs2073618 and rs3134069 on the DR was stronger than that of each SNP alone. The odds ratio (OR) for individuals with CC genotype (rs2073618) and AA genotype (rs3134069) compared with carriers of CG/GG (rs2073618) + AA (rs3134069) was 2.54 (95% CI = 1.26–5.13, ). To conclude, these results indicate that SNPs in the OPG gene may be implicated in the pathogenesis of DR.

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Association of Leptin Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Population

BioMed Research International ◽

10.1155/2020/3789319 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Sha-Sha Tao ◽

Yi-Lin Dan ◽

Guo-Cui Wu ◽

Qin Zhang ◽

Tian-Ping Zhang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Chinese Population ◽

Clinical Manifestations ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Genotype Frequencies ◽

Significant Difference ◽

Plasma Leptin

Background. Recently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population. Methods. We recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination. Results. No significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all P > 0.05 ). Association between the genotype effects of dominant, recessive models was also not found (all P > 0.05 ). No significant difference in plasma leptin levels was detected between RA patients and controls ( P > 0.05 ). Conclusion. Leptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population.

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INTERLEUKIN (IL) 12, IL-23 AND IL-23 RECEPTOR IN ANKYLOSING SPONDYLITIS PATHOPHYSIOLOGY

Romanian Journal of Rheumatology ◽

10.37897/rjr.2015.1.1 ◽

2015 ◽

Vol 24 (1) ◽

pp. 5-13

Author(s):

Marius Cherciu ◽

◽

Laura Ioana Cherciu ◽

Mihai Bojinca ◽

Teodora Serban ◽

...

Keyword(s):

T Cells ◽

Ankylosing Spondylitis ◽

Inflammatory Arthritis ◽

Serum Levels ◽

Nucleotide Polymorphisms ◽

Sacroiliac Joints ◽

Single Nucleotide ◽

Chronic Inflammatory Arthritis ◽

Point Of Interest

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis which involves mainly the spine and the sacroiliac joints, but also the peripheral joints and non-articular structures. IL-12 and IL-23 are heterodimeric cytokines sharing a common p40 subunit. Studies showed than IL-12 is essential for Th1 differentiation while IL-23 promotes a particular subset of T cells characterized by IL-17 production, called Th17. Since the association of IL-23R with AS was reported, the scientific interest has focused on identifying new single nucleotide polymorphisms (SNPs), present in the coding genes for IL-12/IL-23 subunits and their receptors, that increase the susceptibility for AS. Another point of interest for researchers was to investigate if the identified gene variants modify the gene expression of the respective interleukins and/or their receptors, whether that refers to their mRNA expression, their serum levels or the expression of the receptors on the surface of T cells. Given the increasing amount of data that suggests the pivotal role of the IL-23/Th17 axis in AS pathophysiology, new promising therapies, designed to interfere with these pathways, are now in development.

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Effect of NPC1L1 and HMGCR Genetic Variants With Premature Triple-Vessel Coronary Disease

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.704501 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xueyan Zhao ◽

Jingjing Xu ◽

Xiaofang Tang ◽

Keyong Huang ◽

Jiawen Li ◽

...

Keyword(s):

Genetic Variants ◽

Recessive Model ◽

Nucleotide Polymorphisms ◽

Dominance Model ◽

Single Nucleotide ◽

Vessel Disease ◽

Triple Vessel Disease ◽

Increased Risk ◽

Codominant Model ◽

Niemann Pick

Background: Both Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) play a key role on dyslipidaemia. We aim to evaluate whether NPC1L1 and HMGCR genetic variants are associated with susceptibility of premature triple-vessel disease (PTVD).Methods: Four single-nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183, and rs2073547) of NPC1L1; and three SNPs (rs12916, rs2303151, and rs4629571) of HMGCR were genotyped in 872 PTVD patients (males ≤ 50 years old and females ≤ 60 years old), and 401 healthy controls.Results: After adjusting for age and sex, rs12916 of HMGCR was associated with the risk of PTVD in dominance model [odds ratio (OR) = 1.68, 95% confidence intervals (CI): 1.29–2.18, P < 0.001], recessive model (OR = 1.43, 95% CI: 1.08–1.90, P = 0.013) and codominant model (OR = 1.38, 95% CI: 1.17–1.63, P < 0.001); meanwhile, rs4720470 of NPC1L1 was related to increased risk of PTVD in recessive model (OR = 1.74, 95% CI: 1.14–2.74, P = 0.013). Patients who carried both variant rs4720470 and rs12916 also had the risk of PTVD (P < 0.001); however, there were no correlation between these SNPs and the SNYTAX score (all P > 0.05).Conclusions: This is the first report that rs4720470 is a novel polymorphism of the NPC1L1 gene associated with PTVD, and rs12916 of HMGCR gene appears to be a strong genetic marker of PTVD. Our study may improve the early warning, therapeutic strategies and drug development of PTVD.

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Association of Interleukin-10 gene polymorphisms with ankylosing spondylitis

Clinical & Investigative Medicine ◽

10.25011/cim.v34i6.15898 ◽

2011 ◽

Vol 34 (6) ◽

pp. 370 ◽

Cited By ~ 7

Author(s):

Chengyu Lv ◽

Yingzheng Wang ◽

Jinqin Wang ◽

Haining Zhang ◽

Hao Xu ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Single Nucleotide Polymorphisms ◽

Odds Ratio ◽

Serum Levels ◽

Interleukin 10 ◽

Enzyme Linked Immunosorbent Assay ◽

Snp Analysis ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

Objective: Genetic polymorphisms of the Interleukin-10 (IL-10) promoter have been implicated in several autoimmune diseases, including seronegative spondyloarthropathies. This study investigated whether single nucleotide polymorphisms (SNPs) and haplotypes of IL-10 are associated with ankylosing spondylitis (AS), a common subtype of spondyloarthritis (SpA). Methods: The serum levels of IL-10 were measured with an enzyme-linked immunosorbent assay (ELISA). The single nucleotide polymorphisms (SNPs) at positions -1082A/G, -819C/T and -592C/A in the IL-10 gene promoter were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: 110 AS patients and 120 ethnic-matched healthy controls were included in this study. The serum levels of IL-10 were significantly higher in AS patients than healthy controls (Z=-10.9, P < 0.001). Single SNP analysis showed no significant differences in the allelic and genotypic frequencies of -592A/C between the AS patients and healthy controls. No -1082GG genotype was found in this study. An increased frequency of -1082G allele was noted in AS patients (P=0.047). In a logistic regression analysis, the -1082AG genotype was associated with an odds ratio of 1.993 (95%CI, 1.046-3.800, P=0.034) for AS. And the -819CC genotype was associated with an odds ratio of 3.125 (95%CI, 1.246-7.836, P=0.015) for AS. Furthermore, haplotype analysis revealed that GCC haplotype was associated with a significantly increased risk of AS as compared with the ATA haplotype (OR=2.19; 95% CI, 1.13-4.26; P=0.02). Conclusion: Our results indicate that the gene haplotype of IL-10 can contribute to the susceptibility to AS in a Chinese population.

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Multigenic control of serum adiponectin levels: evidence for a role of the APM1 gene and a locus on 14q13

Physiological Genomics ◽

10.1152/physiolgenomics.00122.2004 ◽

2004 ◽

Vol 19 (2) ◽

pp. 170-174 ◽

Cited By ~ 54

Author(s):

C. Menzaghi ◽

T. Ercolino ◽

L. Salvemini ◽

A. Coco ◽

S. H. Kim ◽

...

Keyword(s):

Significant Proportion ◽

Serum Levels ◽

Epidemiological Studies ◽

Serum Adiponectin ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Nuclear Families ◽

Variance Components Analysis

Adiponectin is a circulating enhancer of insulin action that is secreted by the adipose tissue. In epidemiological studies, serum levels of this protein predict the risk of type 2 diabetes and cardiovascular events. Serum adiponectin levels have been associated with variants at the adiponectin (APM1) and PPARγ2 loci and have also been linked to markers on 5p15 and 14q13. We investigated the role of these four loci in regulating serum adiponectin in a Caucasian population from Italy. Four haplotype-tagging single-nucleotide polymorphisms (ht-SNPs) (−11377 C>G, −4041 A>C, +45 T>G, and +276 G>T) at the APM1 locus and the PPARγ2 Pro12Ala polymorphism were examined for association with serum adiponectin in 413 unrelated, nondiabetic individuals. Of the five SNPs tested, +276G>T was the only one to be associated with serum adiponectin ( P = 0.032), with “TT” individuals having higher adiponectin levels than other subjects. In a variance-components analysis of 737 nondiabetic members of 264 nuclear families, adiponectin heritability was 30%, with a small but significant proportion explained by the +276 genotype ( P = 0.0034). Suggestive evidence of linkage with adiponectin levels was observed on chromosome 14q13, with a LOD of 2.92 ( P = 0.000057) after including the APM1 +276 genotype in the model. No linkage was observed at 5p15. Our data indicate a strong genetic control of serum adiponectin. A small proportion of this can be attributed in our population to variability at the APM1 locus, but an as yet unidentified gene on 14q13 appears to play a much bigger role.

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Haplotypes in the GC, CYP2R1 and CYP24A1 Genes and Biomarkers of Bone Mineral Metabolism in Older Adults

Nutrients ◽

10.3390/nu14020259 ◽

2022 ◽

Vol 14 (2) ◽

pp. 259

Author(s):

Ana Fernández-Araque ◽

Andrea Giaquinta-Aranda ◽

Carmelo Moreno-Sainz ◽

María Cruz Martínez-Martínez ◽

Verónica Velasco-González ◽

...

Keyword(s):

Vitamin D ◽

Genetic Variants ◽

Mineral Metabolism ◽

Serum Levels ◽

Codominant Model ◽

Significant Difference ◽

Candidate Gene Studies ◽

Phosphorus Levels

Candidate gene studies have analyzed the effect of specific vitamin D pathway genes on vitamin D availability; however, it is not clear whether genetic variants also affect overall bone metabolism. This study evaluated the association between genetic polymorphisms in GC, CYP2R1 and CYP24A1 and serum levels of total 25(OH)D, iPTH and other mineral metabolism biomarkers (albumin, total calcium and phosphorus) in a sample of 273 older Spanish adults. We observed a significant difference between CYP2R1 rs10741657 codominant model and total 25(OH)D levels after adjusting them by gender (p = 0.024). In addition, the two SNPs in the GC gene (rs4588 and rs2282679) were identified significantly associated with iPTH and creatinine serum levels. In the case of phosphorus, we observed an association with GC SNPs in dominant model. We found a relationship between haplotype 2 and 25(OH)D levels, haplotype 4 and iPTH serum levels and haplotype 7 and phosphorus levels. In conclusion, genetic variants in CYP2R1 and GC could be predictive of 25(OH)D and iPTH serum levels, respectively, in older Caucasian adults. The current study confirmed the role of iPTH as one of the most sensitive biomarkers of vitamin D activity in vivo.

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