No Association of Eight TNFAIP3 Single Nucleotide Variants to Rheumatoid Arthritis in Native Mexicans

Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disease of autoimmune origin associated with many genetic traits, including genes related to the control of inflammation. The A20 protein, encoded by the TNFAIP3 gene, is a negative regulator of NF-kB-mediated inflammation. Several single nucleotide variants (SNVs) of TNFAIP3 are associated with susceptibility to RA in different ethnic groups, but not in Chileans, the only Latin Americans studied thus far. Objective. To examine the association of eight TNFAIP3 SNVs, four of them not previously studied, with RA in Mexican patients. Materials . We studied 471 RA patients (ACR-EULAR 2010) and eight TNFAIP3 SNVs: including, rs10499194C/T, rs6920220G/A and rs2230926T/G, which are associated with RA in European and Asian patients, in addition to rs373421182G/C, rs139054966T/G, rs5029924C/T, rs59693083A/G and rs61593413T/A, not previously examined in RA. All SNVs were evaluated by means of an allelic discrimination assay and TaqMan probes. Results. The allelic and genotypic frequencies of all SNVs examined were similar between cases and controls, and none of them was associated with RA under the allelic, codominant, dominant, and recessive models was observed. Conclusion. Our data indicate that the TNFAIP3 SNVs evaluated herein are not risk factors for RA in Mexican subjects.

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Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase 1 Influenced the Age Onset of Parkinson’s Disease

10.20944/preprints202009.0470.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Nóra Török ◽

Rita Maszlag-Török ◽

Kinga Molnár ◽

Zoltán Szolnoki ◽

Ferenc Somogyvári ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Subgroup Analysis ◽

Snp Analysis ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Allelic Discrimination Assay ◽

Allelic Discrimination ◽

Single Nucleotide ◽

Indoleamine 2,3 Dioxygenase ◽

Tryptophan Dioxygenase

Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson’s disease (PD). The first rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. An increasing number of single nucleotide polymorphisms (SNPs) have been identified in a population of PD. However, little is known if genetic variations of the IDO contribute to disturbance of the KYN metabolism in and the pathogenesis of PD. SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.

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ADIPOQ single nucleotide polymorphisms and breast cancer in northeastern Mexican women

BMC Medical Genetics ◽

10.1186/s12881-020-01125-8 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Ricardo M. Cerda-Flores ◽

Karen Paola Camarillo-Cárdenas ◽

Gabriela Gutiérrez-Orozco ◽

Mónica Patricia Villarreal-Vela ◽

Raquel Garza-Guajardo ◽

...

Keyword(s):

Breast Cancer ◽

Single Nucleotide Polymorphisms ◽

Mexican Women ◽

Genotype Distribution ◽

Nucleotide Polymorphisms ◽

Allelic Discrimination Assay ◽

Allelic Discrimination ◽

Single Nucleotide ◽

Significant Difference ◽

Hardy Weinberg Equilibrium

Abstract Background Adiponectin gene (ADIPOQ) polymorphisms have been shown to affect adiponectin serum concentration and some have been associated with breast cancer (BC) risk. The aims of this study were to describe the frequency of single nucleotide polymorphisms (SNPs) of ADIPOQ in Mexican women with BC and to determine if they show an association with it. Methods DNA samples from 397 patients and 355 controls were tested for the ADIPOQ gene SNPs: rs2241766 (GT) and rs1501299 (GT) by TaqMan allelic discrimination assay. Hardy–Weinberg equilibrium (HWE) was tested. Multiple SNP inheritance models adjusted by age and body mass index (BMI) were examined for the SNP rs1501299. Results We found that in the frequency analysis of rs1501299 without adjusting the BMI and age, the genotype distribution had a statistically significant difference (P = 0.003). The T allele was associated with a BC risk (OR, 1.99; 95% CI 1.13–3.51, TT vs. GG; OR, 1.53; 95% CI 1.12–2.09, GT vs. GG). The SNP rs2241766 was in HW disequilibrium in controls. In conclusion, the rs1501299 polymorphism is associated with a BC risk. Conclusions Identification of the genotype of these polymorphisms in patients with BC can contribute to integrate the risk profile in both patients and their relatives as part of a comprehensive approach and increasingly more personalized medicine.

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Integration of single nucleotide variants and whole-genome DNA methylation profiles for classification of rheumatoid arthritis cases from controls

Heredity ◽

10.1038/s41437-020-0301-4 ◽

2020 ◽

Vol 124 (5) ◽

pp. 658-674 ◽

Cited By ~ 1

Author(s):

Mahmoud Amiri Roudbar ◽

Mohammad Reza Mohammadabadi ◽

Ahmad Ayatollahi Mehrgardi ◽

Rostam Abdollahi-Arpanahi ◽

Mehdi Momen ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Dna Methylation ◽

Whole Genome ◽

Single Nucleotide Variants ◽

Single Nucleotide

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Association of HER1 and HER2 Gene Variants in the Predisposition of Colorectal Cancer

Journal of Oncology ◽

10.1155/2021/6180337 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Ibrahim O. Alanazi ◽

Jilani Purusottapatnam Shaik ◽

Narasimha Reddy Parine ◽

Nahla A. Azzam ◽

Othman Alharbi ◽

...

Keyword(s):

Colorectal Cancer ◽

Health Concern ◽

Nucleotide Polymorphism ◽

Her2 Gene ◽

Allelic Discrimination Assay ◽

Allelic Discrimination ◽

Single Nucleotide ◽

Major Health ◽

Risk Of Cancer ◽

Control Study

Background. Colorectal cancer (CRC) is a major health concern worldwide. A series of sequential accumulation of genetic and epigenetic changes are responsible for the initiation and progression of diseases via the normal > adenoma > carcinoma sequence. Genetic variants in crucial cancer-causing genes are known to mediate the risk of cancer. Objective. In this case-control study, we examined single nucleotide polymorphism (SNP) in HER1 (rs763317 and rs3752651) and HER2 (rs1136201 and rs1058808) genes to assess their role in the susceptibility of CRC in a Saudi population. Methods. TaqMan allelic discrimination assay was utilized to identify the genotypes in 163 normal and 143 CRC patients. Results. In the overall analysis, the rs3752651 and rs1136201 were significantly associated with the risk of CRC. Although none of the examined SNPs had any impact on the age at which CRC was diagnosed, interestingly, three SNPs showed a significant association based on gender. The rs3752651 conferred significant protection only in men, whereas rs1136201 diminished the risk and rs1058808 considerably increased the susceptibility of CRC only in women. Conclusions. Our result suggests that these SNPs in HER1 and HER2 after validation in larger cohorts of different ethnicities may be utilized as genetic screening markers for predicting colorectal cancer predisposition.

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Single Nucleotide Polymorphisms of Indoleamine 2,3-Dioxygenase Influenced the Age Onset of Parkinson’s Disease

10.20944/preprints202010.0172.v2 ◽

2021 ◽

Author(s):

Nóra Török ◽

Rita Maszlag-Török ◽

Kinga Molnár ◽

Zoltán Szolnoki ◽

Ferenc Somogyvári ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Subgroup Analysis ◽

Snp Analysis ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Allelic Discrimination Assay ◽

Allelic Discrimination ◽

Single Nucleotide ◽

Indoleamine 2,3 Dioxygenase ◽

Tryptophan Dioxygenase

Aims Earlier studies reported alterations of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism in Parkinson’s disease (PD). The first rate-limiting enzymes indoleamine 2,3- dioxygenase (IDO) and tryptophan dioxygenase were observed upregulated, resulting elevated KYN/TRP ratios in the serum and cerebrospinal fluid samples of patients with PD. An increasing number of single nucleotide polymorphisms (SNPs) has been identified in a population of PD. However, little is known if genetic variations of the IDO contribute to disturbance of the KYN metabolism in and the pathogenesis of PD. Main methods SNP analysis of IDO1 was performed by allelic discrimination assay with fluorescently labelled TaqMan probes and a subgroup analysis was conducted according to the age of PD onset. The frame shifts variant rs34155785, intronic variant rs7820268, and promotor region variant rs9657182 SNPs of 105 PD patients without comorbidity were analyzed and compared to 129 healthy controls. Key findings No significant correlation was found in three SNPs between PD patients and healthy controls. However, the subgroup analysis revealed that A alleles of rs7820268 SNP or rs9657182 SNP carriers contribute to later onset of PD than non-carriers. Significance The study suggested that SNPs of IDO1 influenced the age onset of PD and genotyping of SNPs in certain alleles potentially serves as a risk biomarker of PD.

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TNFAIP3 Gene Polymorphisms in Three Common Autoimmune Diseases: Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Primary Sjogren Syndrome—Association with Disease Susceptibility and Clinical Phenotypes in Italian Patients

Journal of Immunology Research ◽

10.1155/2019/6728694 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

C. Ciccacci ◽

A. Latini ◽

C. Perricone ◽

P. Conigliaro ◽

S. Colafrancesco ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Systemic Lupus Erythematosus ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Variant Allele ◽

Italian Population ◽

Systemic Lupus ◽

Allelic Discrimination Assay ◽

Allelic Discrimination ◽

Necrosis Factor Alpha

Autoimmune diseases (AIDs) are complex diseases characterized by persistent or recurrent inflammation, alteration of immune response, and production of specific autoantibodies. It is known that different AIDs share several susceptibility genetic loci. Tumor necrosis factor alpha inducible protein 3 (TNFAIP3) encodes the ubiquitin-modifying enzyme A20, which downregulates inflammation by restricting NF-κB, a transcription factor that regulates expression of various proinflammatory genes. Variants in TNFAIP3 gene have been described as associated with susceptibility to several AIDs. Here, we analyzed two TNFAIP3 polymorphisms in Italian patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjogren’s syndrome (pSS), to verify if the genetic variability of TNFAIP3 gene is involved in genetic predisposition to AIDs also in the Italian population. We recruited 313 SLE patients, 256 RA patients, 195 pSS patients, and 236 healthy controls. Genotyping of rs2230926 and rs6920220 in TNFAIP3 gene was performed by an allelic discrimination assay. We carried out a case/control association study and a genotype/phenotype correlation analysis. A higher risk to develop SLE was observed for rs2230926 (P=0.02, OR=1.92). No association was observed between this SNP and the susceptibility to pSS or RA. However, the rs2230926 variant allele seems to confer a higher risk to develop lymphoma in pSS patients, while in RA patients, the presence of RF resulted significantly associated with the variant allele. Regarding the rs6920220 SNP, we observed a significant association of the variant allele with SLE (P=0.03, OR=1.53), pSS (P=0.016, OR=1.69), and RA (P=0.0001, OR=2.35) susceptibility. Furthermore, SLE patients carrying the variant allele showed a higher risk to develop pericarditis, pleurisy, and kidney complications. Our results support the importance of the TNFAIP3 gene variant role in the development of different autoimmune diseases in the Italian population and furtherly confirm a sharing of genetic predisposing factors among these three pathologies.

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Folate metabolic pathway single nucleotide polymorphisms: a predictive pharmacogenetic marker of methotrexate response in Indian (Asian) patients with rheumatoid arthritis

Pharmacogenomics ◽

10.2217/pgs.15.145 ◽

2015 ◽

Vol 16 (18) ◽

pp. 2019-2034 ◽

Cited By ~ 30

Author(s):

Yogita Ghodke-Puranik ◽

Amrutesh S Puranik ◽

Pooja Shintre ◽

Kalpana Joshi ◽

Bhushan Patwardhan ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Single Nucleotide Polymorphisms ◽

Metabolic Pathway ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Asian Patients

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Association of the 6q23 region with the rate of joint destruction in rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/ard.2008.106161 ◽

2009 ◽

Vol 69 (3) ◽

pp. 567-570 ◽

Cited By ~ 20

Author(s):

Hans Ulrich Scherer ◽

Michael P M van der Linden ◽

Fina A S Kurreeman ◽

Gerrie Stoeken-Rijsbergen ◽

Saskia le Cessie ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Severe Disease ◽

Joint Destruction ◽

Joint Damage ◽

Negative Regulator ◽

Nucleotide Polymorphisms ◽

Gene Encoding ◽

Single Nucleotide ◽

Factor Α

BackgroundTwo novel genetic polymorphisms on chromosome 6q23 are associated with susceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close to the gene encoding tumour necrosis factor α-induced protein 3 (TNFAIP3). TNFAIP3 is a negative regulator of NF-κB and is involved in inhibiting TNF-receptor-mediated signalling effects. Interestingly, the initial associations were detected in patients with longstanding RA. However, no association was found for rs10499194 in a Swedish cohort with early arthritis. This might be caused by over-representation of patients with severe disease in cohorts with longstanding RA.ObjectiveTo analyse the effect of the 6q23 region on the rate of joint destruction.MethodsFive single nucleotide polymorphisms in 6q23 were genotyped in 324 Dutch patients with early RA. Genotypes were correlated with progression of radiographic joint damage for a follow-up time of 5 years.ResultsTwo polymorphisms (rs675520 and rs9376293) were associated with severity of radiographic joint damage in patients positive for anti-citrullinated protein/peptide antibodies (ACPA). Importantly, the effects were present after correction for confounding factors such as secular trends in treatment.ConclusionsThese data associate the 6q23 region with the rate of joint destruction in ACPA+ RA.

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A Single Nucleotide Polymorphism (rs4236480) inTRPV5Calcium Channel Gene Is Associated with Stone Multiplicity in Calcium Nephrolithiasis Patients

Mediators of Inflammation ◽

10.1155/2015/375427 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 12

Author(s):

Anas Khaleel ◽

Mei-Shin Wu ◽

Henry Sung-Ching Wong ◽

Yu-Wen Hsu ◽

Yii-Her Chou ◽

...

Keyword(s):

Kidney Stone ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Transient Receptor Potential Vanilloid ◽

Allelic Discrimination Assay ◽

Allelic Discrimination ◽

Single Nucleotide ◽

Functional Roles ◽

Potential Association ◽

Transient Receptor

Nephrolithiasis is characterized by calcification of stones in the kidneys from an unknown cause. Animal models demonstrated the functional roles of the transient receptor potential vanilloid member 5 (TRPV5) gene in calcium renal reabsorption and hypercalciuria. Therefore,TRPV5was suggested to be involved in calcium homeostasis. However, whether genetic polymorphisms ofTRPV5are associated with kidney stone multiplicity or recurrence is unclear. In this study, 365 Taiwanese kidney-stone patients were recruited. Both biochemical data and DNA samples were collected. Genotyping was performed by a TaqMan allelic discrimination assay. We found that aTRPV5polymorphism (rs4236480) was observed to be associated with stone multiplicity of calcium nephrolithiasis, as the risk of stone multiplicity was higher in patients with the TT+CT genotype than in patients with the CC genotype(p=0.0271). In summary, despite the complexity of nephrolithiasis and the potential association of numerous calcium homeostatic absorption/reabsorption factors,TRPV5plays an important role in the pathogenesis of calcium nephrolithiasis.

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Effect of CYP3A5 Genotypes on the Pharmacokinetics of Carbamazepine when used as Monotherapy or Co-Administered with Phenytoin, Phenobarbital or Valproic Acid in Thai Patients

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3q888 ◽

2013 ◽

Vol 16 (4) ◽

pp. 502 ◽

Cited By ~ 11

Author(s):

Duangchit Panomvana ◽

Tharathorn Traiyawong ◽

Somchai Towanabut

Keyword(s):

Valproic Acid ◽

Real Time ◽

Statistical Significance ◽

Pharmacokinetic Parameters ◽

Therapeutic Drug ◽

Allelic Discrimination Assay ◽

Allelic Discrimination ◽

Single Nucleotide ◽

Drug Concentrations ◽

Polymerase Chain

Purpose: To determine the effects of CYP3A5 polymorphisms on carbamazepine (CBZ) pharmacokinetic parameters when CBZ is used either as monotherapy or co-administered with phenytoin (PHT), phenobarbital (PB) or valproic acid (VPA). Methods: Retrospective data were collected from an electronic database and medical records. Blood samples were obtained and drug concentrations analyzed as a part of routine therapeutic drug monitoring (TDM). Screening for wild-type CYP3A5*1 and CYP3A5*3 single nucleotide polymorphism (rs776746) by allelic discrimination assay using real-time polymerase chain reaction technique (real-time PCR) was performed. Pharmacokinetic parameters of CBZ; clearance and dose-adjusted CBZ levels in patients with different genotypes were calculated and compared. Results: Of the 70 patients assessed, 8 (11%) patients were homozygous CYP3A5*1/*1, 28 (40%) patients were heterozygous CYP3A5*1/*3, and 34 (49%) patients were homozygous CYP3A5*3/*3. The CBZ clearance and dose-adjusted CBZ levels did not significantly differ between patients with CYP3A5*1 and CYP3A5*3 alleles when CBZ was used as monotherapy. For patients who used CBZ in combination with an enzyme-inducing antiepileptic drug (AED: PHT or PB), individuals carrying the CYP3A5*1 allele (CYP3A5 expressers) showed a trend of having higher CBZ clearance and lower dose-adjusted CBZ level as compared to individuals carrying the CYP3A5*3 allele, even though no statistical significance was recorded. Nevertheless, it was observed that AEDs significantly increased CBZ clearance only in patients carrying the active CYP3A5*1 allele. Conclusions: When CBZ was used in combination with enzyme-inducing AED, CYP3A5 expressers yielded a trend toward greater susceptibility to change in CBZ clearance and showed lower dose-adjusted CBZ levels compared to CYP3A5 non-expressers. The dosage regimen should be adjusted accordingly to gain a better clinical outcome.This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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