Search for genetic markers of predisposition to psoriasis and psoriatic arthritis

Psoriasis (PS) and psoriatic arthritis (PsA) are interrelated diseases that occur in approximately 30% of patients and are characterized by the presence of a systemic inflammatory reaction that occurs as a result of a violation of the functional state of the immune system. With the advent of new technologies, several new pro-inflammatory cytokines, such as IL-23, IL-31, and IL-33, which play an important role in the pathogenesis of the psoriatic process, have been discovered and characterized. It was determined that single nucleotide polymorphisms (SNPs) in the promoter regions of the IL23, IL31 and IL33 genes play an important role in controlling the expression of relevant cytokines involved in the immunopathogenesis of psoriatic disease. The purpose of the study: to analyze the distribution of genotypes and allelic variants of polymorphisms of the IL23A (rs2066808), IL23R (rs2201841), IL31 (rs7977932) and IL33 (rs7044343), in order to search for genetic markers of predisposition to psoriasis and psoriatic arthritis. Materials and methods. The genotyping of the patients was conducted: psoriasis (PS, n = 77), median age 31.0 years (27.0-43.0), psoriatic arthritis (PsA, n = 99), median age 49.0 years (39.0-56.0) and practically healthy residents of Krasnoyarsk (n = 103), a median age of 32.0 years (24.0-38.0). DNA was isolated from whole venous blood using a standard sorbent kit. Genotyping of single nucleotide polymorphisms IL23A (rs2066808), IL23R (rs2201841), IL31 (rs7977932), IL33 (rs7044343) was carried out using real-time PCR using specific oligonucleotide primers and fluorescentlylabeled probes. Results and discussion. The frequencies of allelic variants of the studied cytokine genes in the control group obtained during the study correspond to their distribution in Caucasoid populations – the alleles IL23A * T, IL23R * T, IL31 * C, IL33 * C prevail. When comparing the distribution frequency of allelic variants of the IL23A, IL23R, IL31, IL33 genes, we did not obtain statistically significant differences between patients and the control group. Conclusions. Despite the fact that when comparing the distribution frequency of allelic variants of the IL23A, IL23R, IL31, IL33 genes, we did not obtain statistically significant differences between the patients and the control group, there are results worthy of attention. So, in patients with PS, the frequency of the C * IL23A allelic variant (rs2066808) is lower than in the population sample, which may indicate its specific role in relation to the development of the disease. All this dictates the need to continue research with the assessment of other SNPs and increase the sample of patients in search of potential genetic markers of psoriatic disease.

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3321 European Ancestry as a Risk Factor for Atrial Fibrillation in Puerto Rican Hispanics

Journal of Clinical and Translational Science ◽

10.1017/cts.2019.28 ◽

2019 ◽

Vol 3 (s1) ◽

pp. 10-11

Author(s):

Ariel Gonzalez-Cordero ◽

Jorge Duconge-Soler ◽

Ángel López-Candales

Keyword(s):

Atrial Fibrillation ◽

Risk Factor ◽

Single Nucleotide Polymorphisms ◽

Puerto Rican ◽

Population Sample ◽

European Ancestry ◽

Genetic Admixture ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

OBJECTIVES/SPECIFIC AIMS: Consequently, we have decided to evaluate the presence of single nucleotide polymorphism (SNP) previously associated with AF on a European-descent population in an attempt to first identify the most common loci present in the PRH population and then search for specific PRH SNP associated with AF. METHODS/STUDY POPULATION: A secondary analysis of a Puerto Rican population sample (n = 120) from The Pharmacogenetics of Warfarin in Puerto Ricans Study will be performed. We will implement data from the 1000 genome project to establish a control group of healthy PRH population. Will evaluate the presence of 111 known single nucleotide polymorphisms associated with AF in Europeans and determine the frequency in PRH population sample, and validate predictability of such SNPs. Using admixture informatic markers (AIM) analysis will determine the percentage of admixture by Yoruba, Native American and Iberic-European. Statistical analysis will include the use of the Pearson Product-Moment Coefficient correlation analysis and multivariate linear regression. For admixture will use Maximum Likelihood Estimation and Markov Chain Monte Carlo models. RESULTS/ANTICIPATED RESULTS: A higher frequency of AF associated European single nucleotide polymorphisms, and an overall higher percentage of European admixture will be associated with atrial fibrillation in Puerto Rican Hispanic patients. DISCUSSION/SIGNIFICANCE OF IMPACT: Our contributions here are expected to be the elucidation of European ancestry as a risk factor for AF. These contributions will be significant because it can provide a robust scientific basis for larger GWAS studies in the Puerto Rican community and further narrow down the mechanism specific to this population. Research in this subject could lead to early identification of patients with high risk of developing atrial fibrillation and further decrease incidence and disease burden in the PRH population. Puerto Rican Hispanics have an exclusive genetic admixture that makes for an appealing research subject that could deliver unique results.

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A pilot replication study of two PER3 single nucleotide polymorphisms as potential genetic markers for morning and evening earliness-lateness

Biological Rhythm Research ◽

10.1080/09291016.2016.1275400 ◽

2017 ◽

Vol 48 (4) ◽

pp. 531-540 ◽

Cited By ~ 6

Author(s):

Vladimir B. Dorokhov ◽

Alexandra N Puchkova ◽

Anton O. Taranov ◽

Petr A. Slominsky ◽

Valentin A. Vavilin ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Genetic Markers ◽

Replication Study ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

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Analysis of 4 Single-Nucleotide Polymorphisms in Relation to Cervical Dysplasia and Cancer Development Using a High-Throughput Ligation-Detection Reaction Procedure

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e31822b6299 ◽

2011 ◽

Vol 21 (9) ◽

pp. 1664-1671 ◽

Cited By ~ 12

Author(s):

Helmut von Keyserling ◽

Thomas Bergmann ◽

Miriam Schuetz ◽

Ursula Schiller ◽

Jonas Stanke ◽

...

Keyword(s):

Cervical Cancer ◽

Single Nucleotide Polymorphisms ◽

Genetic Markers ◽

Cervical Dysplasia ◽

Semantic Integration ◽

Cancer Development ◽

Large Sample Size ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Genetic Characteristics

BackgroundHost genetic characteristics and environmental factors may correlate with risk for cervical cancer development. Here we describe a retrospective screening study for single nucleotide polymorphisms (SNPs) in genetic markersTP53, MTHFR, CYP1A1,andCYP2E1in 749 patients.MethodsA multiplex ligation-dependent polymerase chain reaction approach was applied. We used archived material from human papillomavirus tests and correlated SNP genotypes to the corresponding clinical data. Semantic integration was used to identify and evaluate the clinical status from electronic health records.ResultsAn association with cervical cancer and high-grade dysplasia was found for the rare homozygous CC genotype (rs4646903) inCYP1A1(odds ratio [OR], 8.862). Odds ratios were also significantly elevated for heterozygousMTHFRCT genotype (rs1801133; OR, 1.457). No significant association was found inTP53(rs1042522) andCYP2E1(rs3813867). In addition, we found smokers at higher risk (OR, 2.688) and identified pregnancies as a significant risk factor (OR, 1.54).ConclusionsOur protocol enables a feasible way for further retrospective large sample size evaluation of potential genetic markers. This study revealed genetic associations of a rare SNP genotype with cervical dysplasia in one of the largest patient sample to date that warrants further investigation.

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Genotyping of Essential Hypertension Single-Nucleotide Polymorphisms by a Homogeneous PCR Method with Universal Energy Transfer Primers

Clinical Chemistry ◽

10.1093/clinchem/48.12.2131 ◽

2002 ◽

Vol 48 (12) ◽

pp. 2131-2140 ◽

Cited By ~ 66

Author(s):

Chikh Bengra ◽

Theodore E Mifflin ◽

Yuri Khripin ◽

Paolo Manunta ◽

Scott M Williams ◽

...

Keyword(s):

Essential Hypertension ◽

Single Nucleotide Polymorphisms ◽

Restriction Endonucleases ◽

Control Group ◽

Italian Population ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Hypertensive Patients ◽

Unique Restriction ◽

Set Up

Abstract Background: Human hypertension is a complex, multifactorial disease with a heritability of more than 30–50%. A genetic screening test based on analysis of multiple single-nucleotide polymorphisms (SNPs) to assess the likelihood of developing hypertension would be helpful for disease management. Methods: Tailed allele-specific primers were designed to amplify by PCR six biallelic SNP loci [three in G protein-coupled receptor kinase type 4 (GRK4): R65L, A142V, and A486V; two in angiotensinogen: −6G→A and M235T; and one in aldosterone synthase: −344C→T] associated with essential hypertension. PCRs of SNP loci were coupled (via a common sequence of 21 nucleotide tails) to incorporate Universal Amplifluor™ primers labeled with fluorescein or sulforhodamine in a homogeneous format. Use of Amplifluors in SNP PCRs produced labeled amplicons, the fluorescence of which was quantified by a microplate reader and then analyzed via an Excel macro to provide genotypes for all six SNP loci. Unique restriction endonucleases were identified for five SNP loci that could independently confirm homogeneous PCR results when needed. Results: We developed six homogeneous PCR assays that were set up, performed, and fluorometrically analyzed in 96-well microplates. Allele frequencies were determined for six SNPs in 60 Italian hypertensive patients and a control group of 60 normotensive persons. A significant correlation (P = 0.034) between one SNP [GRK4 (A486V)] and the hypertensive patients was observed. Genotyping results for five of six SNPs were confirmed by digesting corresponding amplicons with locus-specific restriction endonucleases. Conclusions: We developed a simple and homogeneous fluorescent protocol that has been used to determine the SNP genotype for six loci in a population of hypertensive and normotensive persons. We also observed a significant association (P = 0.034) between one SNP (A486V) and an Italian population of mildly hypertensive patients.

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Association of single-nucleotide polymorphisms in the ESR2 and FSHR genes with poor ovarian response in infertile Jordanian women

Clinical and Experimental Reproductive Medicine ◽

10.5653/cerm.2020.03706 ◽

2021 ◽

Vol 48 (1) ◽

pp. 69-79

Author(s):

Amer Mahmoud Sindiani ◽

Osamah Batiha ◽

Esra’a Al-zoubi ◽

Sara Khadrawi ◽

Ghadeer Alsoukhni ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Statistical Significance ◽

Ovarian Response ◽

Control Group ◽

P Value ◽

Case Group ◽

Nucleotide Polymorphisms ◽

Poor Ovarian Response ◽

Single Nucleotide ◽

Number Of Patients

Objective: Poor ovarian response (POR) refers to a subnormal follicular response that leads to a decrease in the quality and quantity of the eggs retrieved after ovarian stimulation during assisted reproductive treatment (ART). The present study investigated the associations of multiple variants of the estrogen receptor 2 (ESR2) and follicle-stimulating hormone receptor (FSHR) genes with POR in infertile Jordanian women undergoing ART.Methods: Four polymorphisms, namely ESR2 rs1256049, ESR2 rs4986938, FSHR rs6165, and FSHR rs6166, were investigated in 60 infertile Jordanian women undergoing ART (the case group) and 60 age-matched fertile women (the control group), with a mean age of 33.60±6.34 years. Single-nucleotide polymorphisms (SNPs) were detected by restriction fragment length polymorphism and then validated using Sanger sequencing.Results: The p-value of the difference between the case and control groups regarding FSHR rs6166 was very close to 0.05 (p=0.054). However, no significant differences were observed between the two groups in terms of the other three SNPs, namely ESR2 rs1256049, ESR2 rs4986938, and FSHR rs6165 (p=0.561, p=0.433, and p=0.696, respectively).Conclusion: The association between FSHR rs6166 and POR was not statistically meaningful in the present study, but the near-significant result of this experiment suggests that statistical significance might be found in a future study with a larger number of patients.

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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 ◽

10.3390/genes10110890 ◽

2019 ◽

Vol 10 (11) ◽

pp. 890 ◽

Cited By ~ 1

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.

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Association of Maternal and Fetal Single-Nucleotide Polymorphisms in Metalloproteinase (MMP1, MMP2, MMP3, and MMP9) Genes with Preeclampsia

Disease Markers ◽

10.1155/2018/1371425 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Agata Sakowicz ◽

Michalina Lisowska ◽

Lidia Biesiada ◽

Magda Rybak-Krzyszkowska ◽

Agnieszka Gach ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Genetic Markers ◽

Gene Polymorphisms ◽

Pivotal Role ◽

Trophoblast Invasion ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Blood Samples ◽

Implantation Process ◽

Risk Of Preeclampsia

Background. Metalloproteinases (MMPs) play a pivotal role during the process of trophoblast invasion and placentation. The appearance of five functional single-nucleotide polymorphisms (SNP) in the genes of the metalloproteinases most commonly implicated in the implantation process may influence the development of preeclampsia. Methods. Blood samples were collected from 86 mothers and 86 children after preeclampsia and 85 mothers and 85 children with uncomplicated pregnancies. The distribution of genotypes for −1607 1G/2G MMP1, −735 C/T MMP2, −1306 C/T MMP2, −1171 5A/6A MMP3, and −1562C/T MMP9 polymorphisms was determined by RFLP-PCR. Results. The occurrence of 1G/1G MMP1 or 5A/5A MMP3 genotype in the mother or 1G/1G MMP1 or 5A/6A MMP3 genotype in the child is associated with preeclampsia development. Moreover, simultaneous maternal and fetal 1G/1G homozygosity increases the risk of preeclampsia development 2.39-fold and the set of maternal 5A/5A and fetal 5A/6A MMP3 genotypes by over 4.5 times. No association between the carriage of studied MMP2 or MMP9 polymorphisms and the predisposition to preeclampsia was found. Conclusion. The maternal 1G/1G MMP1 and 5A/5A MMP3 and fetal 1G/1G MMP1 and 5A/6A MMP3 gene polymorphisms may be strong genetic markers of preeclampsia, occurring either individually or together.

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Genetic association study of SOX2 gene polymorphisms with high myopia in a Chinese population

European Journal of Ophthalmology ◽

10.1177/1120672120904666 ◽

2020 ◽

pp. 112067212090466

Author(s):

Lan Li ◽

Ying Juan Cui ◽

Yunchun Zou ◽

Liyuan Yang ◽

Ximin Yin ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Chinese Population ◽

High Myopia ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Spherical Equivalent ◽

Chi Square ◽

Single Nucleotide ◽

Sox2 Gene ◽

Chi Square Test

Purpose: The aim of this study is to investigate whether SOX2 gene variants were associated with high myopia in a Chinese population. Methods: This study is conducted using case-control association analysis. This study recruited 83 healthy controls (with binocular spherical equivalent between –0.50 and +0.50 D) and 117 high myopia cases (spherical equivalent > –6.00 D in both eyes). Three single-nucleotide polymorphisms were selected from HapMap database for genotyping by direct sequencing. Statistical software (SPSS 22.0) was used for statistical analysis. The chi-square test was used to examine the difference in the frequency between cases and controls. Results: Genotype distributions in the three single-nucleotide polymorphisms were all in accordance with the Hardy–Weinberg equilibrium. The differences of rs4575941 locus genotype frequency and allele frequency between the case group and the control group were statistically significant (p = .043 and p = .029, respectively). The rs4575941 allele G frequency in the high myopia group was significantly higher than that in the control group with an odds ratio value of 1.579. However, the value of a chi-square test for the trend was 0.029, and after Bonferroni test, the p value was .087. Conclusion: In Chinese population, rs4575941 in SOX2 gene was likely to play some roles in the genetic susceptibility to high myopia; the rs4575941 allele G might be a risk gene for high myopia.

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SINGLE-NUCLEOTIDE POLYMORPHISMS OF CALCIUM-SENSING RECEPTOR ENCODING GENE ASSOCIATED WITH CALCIUM KIDNEY STONE DISEASE IN BABYLON PROVINCE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i2.22064 ◽

2018 ◽

Vol 11 (2) ◽

pp. 417 ◽

Cited By ~ 1

Author(s):

Zahraa Isam ◽

Rabab Omran ◽

Ammad Hassan Mahmood

Keyword(s):

Amino Acid ◽

Single Nucleotide Polymorphisms ◽

Kidney Stone ◽

Stone Disease ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Calcium Sensing Receptor ◽

Single Nucleotide ◽

Kidney Stone Disease ◽

Calcium Sensing

Objective: The calcium-sensing receptor (CASR) is a G-protein-coupled receptor that is mainly expressed in the parathyroid and the kidneys where it regulates parathyroid hormone secretion and renal tubular calcium reabsorption. Inactivating and activating CASR gene due to mutations severally caused hypercalcemia or hypocalcemia disorders. The aim of the study was to investigate the risk factor of CASR rs1801725 (Ala986Ser) patients with renal disease.Method: The blood samples were collected from 100 patients and divided into two groups, each one containing 50 samples; chronic kidney disease and end-stage renal disease, who admitted Merjan Teaching Hospital in Babylon Province, Iraq, from February to July 2016. In addition, healthy persons as a control group (50 samples). Genotyping of CASR single-nucleotide polymorphisms (SNP) was performed using a polymerase chain reaction technique, followed by single-strand conformation polymorphism. Accordingly, these DNA polymorphisms were confirmed using DNA sequencing.Results: The conformational haplotypes of CASR, exon7 NCBI Primer3plus reference were obtained in three patterns, including two, three, and four bands, due to the presence SNPs within the studied region. These SNPs leads to change three amino acid residues of CASR, including amino acid substitutions were Ala 128→ Ser 128, Leu 155→Tye 155, and Leu 156→ Ser 156 that may affect or modified the tertiary structure of the receptor, subsequently the function like the affinity to calcium ion may be effected.Conclusion: These results suggest that the variants of CASR SNP, namely, rs1801725 might be involved in susceptibility to kidney stone disease.

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Correlation between miRNA target site polymorphisms in the 3′ UTR of AVPR1A and the risk of hypertension in the Chinese Han population

Bioscience Reports ◽

10.1042/bsr20182232 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 1

Author(s):

Liuping Zhang ◽

Jinwei Liu ◽

Peng Cheng ◽

Fangchao Lv

Keyword(s):

Single Nucleotide Polymorphisms ◽

Mirna Target ◽

Direct Sequencing ◽

Chinese Han Population ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Single Nucleotide ◽

Han Population ◽

Increased Risk

Abstract We aimed to study the relationship between rs11174811 and rs3803107 single nucleotide polymorphisms (SNPs) in miRNA target sites of the 3′ UTR in the arginine vasopressin receptor 1a gene (AVPR1A) and the risk of hypertension in the Chinese Han population. The genotypes at rs11174811 and rs3803107 were analyzed by direct sequencing in 425 Chinese Han patients with hypertension and 425 healthy subjects. AVPR1A expression was investigated by transfecting miR-526b, miR-375, and miR-186 mimics into human umbilical vein endothelial cells (HUVECs) containing AVPR1A rs11174811 CC, CA/AA and AVPR1A rs3803107 GG, GA/AA genotypes. The A alleles of rs11174811 (adjusted OR = 1.424, 95% CI: 1.231–1.599, P<0.001) and rs3803107 (adjusted OR = 1.222, 95% CI: 1.092–1.355; P=0.001) were high risk factors for hypertension. Plasma levels of miR-526b, miR-375, and miR-186 were higher in the study group than in the control group (P<0.001). The expression levels of AVPR1A mRNA in AVPR1A rs11174811 and rs3803107 mutant HUVECs were higher than those in wild-type cells (t = 8.811, 4.068 and P=0.001, 0.015, respectively). The single nucleotide polymorphisms rs11174811 and rs3803107 in the AVPR1A gene are associated with an increased risk of hypertension in the Chinese Han population. This may be related to the effect of these variants on the regulation of AVPR1A expression by miRNAs.

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