Significant Differences In Allele Frequencies Research Articles

Survey of the association between polymorphisms of CTLA-4 exon 1 49 A/G genes with rheumatoid arthritis in Iran

ABSTRACT Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which suppresses T cell proliferation, is a promising candidate for the susceptibility genes to rheumatic arthritis diseases (RA). This study aims to examine the association between the polymorphisms of the CTLA-4 exon 1(+ 49) genes with RA in the Qazvin city of Iran population. The polymerase chain reaction of genomic DNA-restriction fragment length polymorphism (PCR-RFLP) was applied to genotype the CTLA-4 exon 1(+ 49) polymorphisms in 105 RA patients and 90 control subjects. Laboratory diagnostic tests were also measured for RA and control groups. Our results did not demonstrate a significant difference in allele and genotype frequencies of the CTLA-4 exon 1(+ 49) between RA patients and the control group (p < .0001). There was no significant difference in age at onset, CRP, RF value in patients with RA according to the CTLA-4 polymorphisms; just anti-CCP showed a significant difference. Our data declared that polymorphisms of CTLA-4 exon 1(+ 49) genes are not correlated with RA susceptibility and its clinical and paraclinical manifestations.

Association Between Genetic Polymorphisms of lncRNA NEAT1 and Pulmonary Tuberculosis Risk, Clinical Manifestations in a Chinese Population.

BackgroundRecent studies have shown that abnormal expression of lncRNA NEAT1 is associated with the progression of pulmonary tuberculosis (PTB). The aim of our study was to analyze the relationship between single nucleotide polymorphisms (SNPs) of NEAT1 gene and susceptibility to PTB.MethodsFour SNPs (rs2239895, rs3741384, rs3825071, rs512715) in NEAT1 gene were genotyped in 479 patients with PTB and 476 controls by improved multiple ligase detection reaction (iMLDR) in a Chinese population.ResultsWe found no significant differences in allele and genotype frequencies of NEAT1 gene rs2239895, rs3741384, rs3825071, rs512715 between PTB patients and controls (all P > 0.05). There was no statistically significant association between genotype frequency distribution of dominant model, as well as recessive model, and genetic susceptibility to PTB patients (all P > 0.05). The TT genotype, T allele frequencies of rs3825071 were significantly increased in sputum smear-positive PTB patients when compared to sputum smear-negative PTB patients (P = 0.010, P = 0.003, respectively). Haplotype analysis shown that NEAT1 haplotype frequency was not associated with PTB susceptibility.ConclusionNEAT1 gene polymorphisms were not associated with the risk of PTB in Chinese population, and rs3825071 polymorphism might be related to sputum smear-positive in PTB patients.

Evaluation of the rs35996865 polymorphism of the ROCK1 gene in sepsis.

Sepsis is a complex and serious medical condition resulting from the activation of an innate host response to infections. The etiology of sepsis is complex and can be influenced by genetic susceptibility. The purpose of the present study was to investigate a possible association of Rho-kinase 1 (ROCK1) gene polymorphism with sepsis in a Turkish population. The study group consisted of 100 unrelated patients with sepsis and 100 healthy controls. Genomic DNA was isolated from peripheral leukocytes from EDTA-containing blood using the QIAamp DNA Blood Mini Kit. ROCK1 gene rs35996865 and rs112130712 (Lys1054Arg) polymorphisms were analyzed in genomic DNA using the LightCycler 480 II real-time polymerase chain reaction. There were no significant differences in allele and genotype frequencies for ROCK1 gene rs35996865 polymorphism between the patients with sepsis and control group (p>0.05). Additionally, no association was detected between the rs35996865 polymorphism and mortality in the patient group. No polymorphism was detected with ROCK1 gene rs112130712 (Lys1054Arg) in our study groups. Our data showed that there is no marked association between the rs35996865 polymorphism and sepsis. Therefore, these results suggest that ROCK1 gene rs35996865 polymorphism is not risk factor for the development of sepsis in the Turkish population.

육상투척 선수군에서 ACTN3 유전자의 R577X 다형성과 COMT 유전자의 Val158Met 다형성의 분포

The aim of this study was to compare the genotype and allele distributions of the R577X(C1747T, rs1815739) polymorphism in α-actinin 3(ACTN3) gene and the Val158Met(G/A, rs4680) polymorphism in catechol-O-methyltransferase(COMT) gene between controls and athletes of throwing event in order to search for the useful genetic marker(s) influencing the athletic performance of throwing event. On the whole, seventy eight individuals were included in this study, and they grouped in controls(n=55) and throwers(n=23), respectively. Total genomic DNA was isolated from all subjects, and two genetic polymorphisms in each gene were assayed by SNaPshot method. In the case of the Val158Met polymorphism in COMT gene, there were no significant differences in genotype and allele distributions between controls and throwers, respectively. But, there were the significant differences in both genotype and allele frequencies of the R577X polymorphism in ACTN3 gene between two groups, respectively(p .05). Especially, the frequencies of RR genotype and R allele in this genetic polymorphism were overrepresented in throwers compared to controls, respectively. Thus, these results suggest that the R577X polymorphism in ACTN3 gene is likely to significantly influence the athletic performance of throwing event in at least Koreans. Because the genotype and allele frequencies of each genetic polymorphism can vary by ethnicity with different genetic bacjground, further studies by using other ethnic groups will be needed to replicate our positive association study result observed in the R577X polymorphism of ACTN3 gene.

Identification of functional single nucleotide polymorphisms in the porcine SLC6A4 gene associated with aggressive behavior in weaned pigs after mixing.

Variation in genes of the serotonergic system influences aggressive behavior by affecting serotonin levels in the central and cortical nervous system. SLC6A4 (serotonin transporter) is a master regulator of 5-HT signaling and involved in the regulation of aggressive behavior in humans and rodents. To identify potential functional single nucleotide polymorphisms (SNPs) for the porcine SLC6A4 gene associated with aggressive behavior, a total of 500 pigs (268 barrows and 232 gilts) were selected and mixed in 51 pens. Their behavior was recorded and observed for 72 h after mixing. Based on a composite aggressive score (CAS), the most aggressive and the least aggressive pigs within each pen were selected separately (a total of 204 pigs). Ear tissue was sampled to extract genomic DNA. Eight SNPs in the 5'-flanking region, coding region, and 3'-untranslated region (3'-UTR) of SLC6A4 were genotyped, of which 6 SNPs had significant differences (P < 0.05) in allele frequency between the most aggressive and least aggressive pigs. Luciferase activity was greater in plasmids of genotype GG than plasmids of genotype CC of rs345058216 (P < 0.01). Computational analysis nominated MAZ as putative transcription factor (TF) with higher probability to bind the SLC6A4 promoter at the SNP (rs345058216) site. Also, we demonstrated that MAZ overexpression modulates SLC6A4 promoter activity in allele-specific manner with an in vitro assay. In addition, we demonstrated that SLC6A4 was a direct target of miR-671-5p. The dual luciferase reporter gene assay and cell transfection were performed to examine the role of miR-671-5p in regulating SLC6A4 expression. The luciferase assays revealed that the SNP rs332335871 affects regulation of miR-671-5p in SLC6A4 expression. After overexpression of miR-671-5p in porcine primary neural cells, the SLC6A4 mRNA levels can be significantly reduced. In conclusion, we here found that miR-671-5p and MAZ mediated porcine SLC6A4 expression level, which provides the possible molecular mechanism of aggressive behavior.

Fibroblast growth factor-23 rs7955866 polymorphism and risk of chronic kidney disease

BackgroundA missense gain-of-function fibroblast growth factor-23 (FGF23) gene single nucleotide polymorphism (SNP) (rs7955866) has been associated with FGF23 hypersecretion, phosphaturia, and bone disease. Excess circulating FGF23 was linked with atherosclerosis, hypertension, initiation, and progression of chronic kidney disease (CKD).MethodsThe study included 72 CKD stage 2/3 Egyptian patients (27–71 years old, 37 females) and 26 healthy controls matching in age and sex. Repeated measures of blood pressure were used to quantify hypertension on a semiquantitative scale (grades 0 to 5). Fasting serum urea, creatinine, uric acid, total proteins, albumin, calcium, phosphorus, vitamin D3, intact parathyroid hormone (iPTH), and intact FGF23 (iFGF23) were measured. DNA extracted from peripheral blood leucocytes was used for genotyping of FGF23 rs7955866 SNP using the TaqMan SNP genotyping allelic discrimination method.ResultsMajor causes of CKD were hypertension, diabetic kidney disease, and CKD of unknown etiology. There was no significant difference in minor allele (A) frequency between the studied groups (0.333 in GI and 0.308 in GII). Median (IQR) serum iFGF23 was significantly higher in GI [729.2 (531.9–972.3)] than in GII [126.1 (88.5–152.4)] pg/mL, P < 0.001. Within GI, the minor allele (A) frequency load, coded for codominant inheritance, had a significant positive correlation with both hypertension grade (r = 0.385, P = 0.001) and serum iFGF23 (r = 0.259, P = 0.028). Hypertension grade had a significant positive correlation with serum phosphorus and iFGF23.ConclusionsFor the first time in an Egyptian cohort, we report a relatively high frequency of the rs7955866 SNP. It may remain dormant or become upregulated in response to some environmental triggers, notably dietary phosphorus excess, leading to increased circulating iFGF23 with ensuing hypertension and/or renal impairment. Subjects with this SNP, particularly in the homozygous form, are at increased risk for CKD of presumably “unknown” etiology, with a tendency for early onset hypertension and increased circulating iFGF23 out of proportion with the degree of renal impairment. Large-scale population studies are needed to confirm these findings and explore the role of blockers of the renin–angiotensin–aldosterone system and sodium chloride cotransporters in mitigating hypertension associated with FGF23 excess.

Phenotypic and HLA-DRB1 allele characterization of Swedish cardiac sarcoidosis patients

BackgroundEarly detection and initiation of treatment in cardiac sarcoidosis (CS) is believed to be crucial to reduce morbidity and mortality. The diagnosis of CS is challenging, especially in isolated CS (ICS). Certain human leukocyte antigen (HLA-DRB1) alleles associate with different phenotypes of sarcoidosis. Phenotypic and genotypic characterization of patients with CS may improve our ability to identify patients being at risk for developing CS. Methods87 patients with CS, identified at two Swedish university hospitals were included. Phenotypic characteristics were extracted from the medical records and the patients were HLA-DRB1 typed. ResultsMedian age at diagnosis was 55 years, 37% were women. HLA-DRB1 distribution was similar to a general sarcoidosis population. A majority of patients (51/87) had CS as the first sarcoidosis presentation. They were younger (p = 0.04), more often presenting with ventricular tachycardia (VT) or atrioventricular block (AVB) grade II or III (p < 0.001), had lower left ventricular ejection fraction (LVEF) (p = 0.002), lower serum angiotensin converting enzyme (s-ACE) (p = 0.025), and fewer extra cardiac manifestations (ECM) (p = 0.02) than those presenting with CS later. ConclusionsOf Swedish CS patients, 59% presented with cardiac involvement as first manifestation. They had more severe cardiac symptoms than patients presenting with CS later. This phenotype disclosed less ECM and lower s-ACE thus diagnosis can be missed or delayed. We did not observe significant differences in HLA-DRB1 allele frequency between patients with CS compared to sarcoidosis in general. Awareness of CS as a primary manifestation can enable early detection and adequate intervention.

The Genomic Profile Associated with Risk of Severe Forms of COVID-19 in Amazonian Native American Populations.

Genetic factors associated with COVID-19 disease outcomes are poorly understood. This study aimed to associate genetic variants in the SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1, and ABO genes with the risk of severe forms of COVID-19 in Amazonian Native Americans, and to compare the frequencies with continental populations. The study population was composed of 64 Amerindians from the Amazon region of northern Brazil. The difference in frequencies between the populations was analyzed using Fisher’s exact test, and the results were significant when p ≤ 0.05. We investigated 64 polymorphisms in 7 genes; we studied 47 genetic variants that were new or had impact predictions of high, moderate, or modifier. We identified 15 polymorphisms with moderate impact prediction in 4 genes (ABO, CXCR6, FYCO1, and SLC6A20). Among the variants analyzed, 18 showed significant differences in allele frequency in the NAM population when compared to others. We reported two new genetic variants with modifier impact in the Amazonian population that could be studied to validate the possible associations with COVID-19 outcomes. The genomic profile of Amazonian Native Americans may be associated with protection from severe forms of COVID-19. This work provides genomic data that may help forthcoming studies to improve COVID-19 outcomes.

Health influenced by genetics: A first comprehensive analysis of breast cancer high and moderate penetrance susceptibility genes in the Tunisian population.

Significant advances have been made to understand the genetic basis of breast cancer. High, moderate and low penetrance variants have been identified with inter-ethnic variability in mutation frequency and spectrum. Genome wide association studies (GWAS) are widely used to identify disease-associated SNPs. Understanding the functional impact of these risk-SNPs will help the translation of GWAS findings into clinical interventions. Here we aim to characterize the genetic patterns of high and moderate penetrance breast cancer susceptibility genes and to assess the functional impact of non-coding SNPs. We analyzed BRCA1/2, PTEN, STK11, TP53, ATM, BRIP1, CHEK2 and PALB2 genotype data obtained from 135 healthy participants genotyped using Affymetrix Genome-Wide Human SNP-Array 6.0. Haplotype analysis was performed using Haploview.V4.2 and PHASE.V2.1. Population structure and genetic differentiation were assessed using principal component analysis (PCA) and fixation index (FST). Functional annotation was performed using In Silico web-based tools including RegulomeDB and VARAdb. Haplotype analysis showed distinct LD patterns with high levels of recombination and haplotype blocks of moderate to small size. Our findings revealed also that the Tunisian population tends to have a mixed origin with European, South Asian and Mexican footprints. Functional annotation allowed the selection of 28 putative regulatory variants. Of special interest were BRCA1_ rs8176318 predicted to alter the binding sites of a tumor suppressor miRNA hsa-miR-149 and PALB2_ rs120963 located in tumorigenesis-associated enhancer and predicted to strongly affect the binding of P53. Significant differences in allele frequencies were observed with populations of African and European ancestries for rs8176318 and rs120963 respectively. Our findings will help to better understand the genetic basis of breast cancer by guiding upcoming genome wide studies in the Tunisian population. Putative functional SNPs may be used to develop an efficient polygenic risk score to predict breast cancer risk leading to better disease prevention and management.

A Polymorphism in the BDNF Gene (rs11030101) is Associated With Negative Symptoms in Chinese Han Patients With Schizophrenia.

Objective: This study aimed to investigate the association between brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element binding protein (CREB) gene polymorphisms and schizophrenia. Methods: This study used a case-control design, and diagnoses were made based on the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition criteria. One hundred and thirty-four patients with schizophrenia were recruited from the Third People’s Hospital of Zhongshan City from January 2018 to April 2020. Sixty-four healthy controls were recruited from the same region. Genotypes at the BDNF gene single nucleotide polymorphisms rs11030101, rs2030324, and rs6265 and the CREB gene single nucleotide polymorphisms rs6740584 and rs2551640 were determined using a MassARRAY mass spectrometer. Linkage disequilibrium and haplotype analyses were performed, and genotype and allele frequencies were compared between groups. The positive and negative symptom scale (PANSS) was used to evaluate the association between the BDNF and CREB gene polymorphisms and schizophrenic symptoms. Results: There was no significant difference in genotype or allele frequencies for rs11030101, rs2030324, rs6265, rs6740584, or rs2551640 between schizophrenic patients and controls (p > 0.05). In addition, there were no significant differences in rs11030101, rs2030324, rs6265, rs6740584, or rs2551640 genotype frequencies between the two groups in the dominant, recessive, or over-dominant models (p > 0.05). Three loci in the BDNF gene and two loci in the CREB gene were in a state of strong linkage disequilibrium. The frequency of haplotype AAC (rs11030101/rs2030324/rs626), composed of three loci in the BDNF gene, was significantly increased in schizophrenic patients compared with control subjects. There were significant differences in the subscores of PANSSS for negative symptoms, in patients with different rs11030101 genotypes of the BDNF gene (p < 0.05). There was also significant differences in the PANSS scores for the general symptom G12 (judgment and lack of insight) in patients with different rs6265 genotypes of the BDNF gene (p < 0.05). Conclusion: The BDNF gene rs11030101/rs2030324/rs6265 AAC haplotype was potentially associated with an increased risk of schizophrenia. In addition, genotypes at the rs11030101 and rs6265 loci may affect the negative symptoms and general symptoms of schizophrenic patients, respectively.

Genome-wide scan for selection signatures and genes related to heat tolerance in domestic chickens in the tropical and temperate regions in Asia

Heat stress is one of the major environmental stressors challenging the global poultry industry. Identifying the genes responsible for heat tolerance is fundamentally important for direct breeding programs. To uncover the genetic basis underlying the ambient temperature adaptation of chickens, we analyzed a total of 59 whole genomes from indigenous chickens that inhabit South Asian tropical regions and temperate regions from Northern China. We applied FST and π-ratio to scan selective sweeps and identified 34 genes with a signature of positive selection in chickens from tropical regions. Several of these genes are functionally implicated in metabolism (FABP2, RAMP3, SUGCT, and TSHR) and vascular smooth muscle contractility (CAMK2), and they may be associated with adaptation to tropical regions. In particular, we found a missense mutation in thyroid-stimulating hormone receptor (41020238:G>A) that shows significant differences in allele frequency between the chicken populations of the two regions. To evaluate whether the missense mutation in TSHR could enhance the heat tolerance of chickens, we constructed segregated chicken populations and conducted heat stress experiments using homozygous mutations (AA) and wild-type (GG) chickens. We found that GG chickens exhibited significantly higher concentrations of alanine aminotransferase, lactate dehydrogenase, and creatine kinase than AA chickens under heat stress (35 ± 1°C) conditions (P < 0.05). These results suggest that TSHR (41020238:G>A) can facilitate heat tolerance and adaptation to higher ambient temperature conditions in tropical climates. Overall, our results provide potential candidate genes for molecular breeding of heat-tolerant chickens.

Abstract 43: Prevalence of islet-autoantibodies and monogenic diabetes in children with recent onset type 1 diabetes mellitus: A multicenter study

Background: Previous smaller studies have shown higher prevalence of islet-antibody negative Type 1 diabetes mellitus (T1DM) among Indians compared to Caucasians. Islet-antibody negative (Type 1B) diabetes is not well characterized.Aims and Objectives: To study the prevalence of islet-autoantibodies, characterize type 1B diabetes, and determine the role of enterovirus infections and monogenic diabetes in children and adolescents with recent onset T1DM.Results: Among 111 patients, frequency of islet-autoantibody positivity were: GAD65-73%, IA2-35% and ZnT8-34%. 20 (18%) were negative for all 3 islet-autoantibodies. There were no significant clinical, biochemical or HLA allelic frequency differences between antibody negative and positive group. None of the ninety subjects tested showed evidence of enterovirus infection in serum by RT-PCR. Of the seven Type 1B patients without ketoacidosis tested, 2 had pathogenic mutations: one each in WFS 1 [homozygous c.2006A>G (p.Tyr669Cys)] and HNF4a [heterozygous c.998G>A (p.Arg333His)] loci. An additional 2 subjects had mutations of uncertain significance: one each in WFS 1 [heterozygous c.1522_1523del (p.Tyr508CysfsTer34)] and ABCC 8 [Heterozygous c.3784G>A (p.Ala1262Thr)] loci.Conclusions: A significant proportion of patients with T1DM were negative for islet antibodies at onset, but did not differ clinically or biochemically. Monogenic diabetes was found in a proportion of patients with type 1B diabetes.

The relationship between phosphodiesterase 4D gene polymorphism and coronary heart disease.

Coronary atherosclerotic heart disease is one of the most common heart diseases that seriously endanger human health. The study found that intracellular second messenger CAMP plays an important role in inhibiting the proliferation and migration of vascular smooth muscle and the local inflammatory response at the damaged vessel. Phosphodiesterase 4D (PDE4D) can specifically degrade cAMP. The purpose of this article is to investigate the relationship between phosphodiesterase 4D gene polymorphism and coronary heart disease and the effect of phosphodiesterase 4D gene polymorphism on cardiovascular, using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was used to detect 50 patients with coronary heart disease (ACS group) and 100 patients who were diagnosed with coronary artery disease by coronary angiography at the same time as the control group (NC group). The results of the study showed that the frequencies of AA, AG, and GG genotypes in 150 samples were 25.67%, 54.66%, and 22.67%, respectively, which was consistent with Hard Weber's law (X = 2.186, P = 0.101). The distribution of GG genotype (18% vs. 27%), AA + AG genotype (85% vs. 74%), G (57% vs. 55%), A (43% vs. 45 %) There was no statistically significant difference in allele frequency (P <0.05). From this, it can be seen that the rs918592 polymorphism of the PDE4D gene is not associated with coronary heart disease.

Genetic variation of pharmacogenomic VIP variants in the Chinese Li population: an updated research.

Previous studies have shown that the frequency of very important pharmacogenomic (VIP) genes varies in different populations which leads to the diversities in drug efficacy, safety, and the risk associated with adverse drug reactions (ADRs). The purpose of this study was to identify the distribution differences of VIP variants between the Li population and the other 13 populations. Based on the Pharmacogenomics Knowledgebase database (PhamGKB), we successfully genotyped 52 VIP variants within 27 genes in 200 unrelated Li population. χ2 test was used to evaluate the significant differences of genotype and allele frequencies between the Li and the other 13 populations from 1000 Genomes Project. Our study showed that the genotype frequencies of single nucleotide polymorphisms (SNPs) on KCNH2, ACE, CYP4F2, and CYP2E1 were considerably different between Li and the other 13 populations, especially in rs1805123 (KCNH2), rs4291 (ACE), rs3093105 (CYP4F2), and rs6413432 (CYP2E1) loci. Meanwhile, we found several VIP variants that might alter the drug metabolism of cisplatin-cyclophosphamide (CYP2E1), vitamin E (CYP4F2), asthma amlodipine, chlorthalidone, and lisinopril (ACE) through PharmGKB. We also identified other variants which were associated with adverse effects in isoniazid and rifampicin (CYP2E1; hepatotoxicity). The four loci rs1805123 (KCNH2), rs4291 (ACE), rs3093105 (CYP4F2), and rs6413432 (CYP2E1) provided a reliable basis for the prediction of the efficacy of certain drugs. The study complemented the existed pharmacogenomics information, which could provide theoretical basis for predicting the efficacy of certain drugs in the Li population.

Association of the ADCY9 gene and gene-environmental interaction with the susceptibility to childhood bronchial asthma

To study the association of the single nucleotide polymorphisms (SNPs) of the adenylyl cyclase IX (ADCY9) gene at rs1967309, rs2230739, rs2601814, rs2601825, rs2601796, and rs2283497 loci and gene-environment interaction with childhood bronchial asthma (asthma for short). A total of 123 children with asthma who attended the hospital from March 2019 to September 2021 were enrolled as the asthma group, among whom 84 (68.3%) had mild-to-moderate attacks and 39 (31.7%) had severe attacks. A total of 124 healthy children were enrolled as the control group. The association of the SNPs and haplotypes of the ADCY9 gene at the above 6 loci with the susceptibility to childhood asthma was evaluated. The method of generalized multifactor dimensionality reduction was used to analyze gene-environment interaction. Polymorphisms were observed for the ADCY9 gene at the above six loci in both the asthma and control groups, and there were significant differences in genotype and allele frequencies at the rs1967309 locus between the two groups (P<0.05). There was no significant difference in the distribution frequency of haplotypes TA and GG between the asthma and control groups (P>0.05). The generalized multifactor dimensionality reduction analysis showed interaction between rs1967309 locus and allergen contact (P<0.05), which increased the risk of asthma (OR=1.585, P<0.05). The rs1967309 locus of the ADCY9 gene is associated with the susceptibility to childhood asthma, and the locus and allergen contact have a synergistic effect on the development of asthma.

Association between ТР53, MDM2 and NQO1 gene polymorphisms and viral load among women with human papillomavirus.

The risk of cervical cancer is caused by persistent human papillomavirus (HPV) infection. Cervical cancer is the most frequent cancer among women. Our purpose was to investigate the association between TP53 215C>G (Pro72Arg), MDM2 -410T>G, and NQO1 609C>T gene polymorphisms with a high HPV load and the inf luence of gene-gene interactions on prolonged HPV infection. Eighty-nine women with a high HPV viral load and 114 healthy women were involved in a case–control study. Genotyping for TP53 215C>G (Pro72Arg) and MDM2 -410T>G SNPs was carried out by allele-specif ic PCR and genotyping for NQO1 609C>T was performed by a TaqMan assay. Quantitative analysis of HPV DNA was performed by AmpliSens® HPV HCR screen-titer-FRT test system. Gene-gene interactions were analyzed using the multifactor dimensionality reduction (MDR) method. The study of separate SNPs of MDM2 -410T>G and NQO1 609C>T genes did not reveal any statistically signif icant difference in genotype and allele frequencies among women within the two groups. The frequency of the 215G (72Arg) allele and 215GG (72Arg/ Arg) genotype of the TP53 gene was signif icantly higher in the case group than in the control group (OR = 1.74, 95 % CI = 1.10–2.73; p = 0.02 and OR = 1.97, 95 % CI = 1.13–3.46; p = 0.04, respectively). MDR analysis showed the signif icance of intergenic interactions of the three studied loci TP53 (rs1042522) – MDM2 (rs2279744) – NQO1 (rs1800566) for the formation of a high HPV load (OR = 3.05, 95 % CI = 1.73–5.46; p = 0.0001).

Alcohol consumption, aldehyde dehydrogenase 2 gene rs671 polymorphism, and psoriasis in Taiwan

Background: Although alcohol use has been determined as a predisposing factor for psoriasis, research findings have been inconsistent. Objectives: This study investigated whether alcohol intake is causally linked to psoriasis. Methods: The presence of rs671 polymorphism in the aldehyde dehydrogenase 2 (ALDH2) gene was investigated in 258 psoriasis patients and 605 healthy controls. The rs671 was employed as an instrumental variable for predicting alcohol use. Mendelian randomization (MR) was utilized to assess the causality between genetically determined alcohol consumption and psoriasis using the two-stage least-square (2SLS) approach. A replication study of MR analysis with inverse-variance weighting (IVW), MR-Egger regression, and weighted median methods was performed using openly accessible alcohol consumption and psoriasis summary statistics from the UK Biobank. Results: Between psoriasis and controls, there were no significant differences in genotype and allele frequencies for the ALDH2 rs671 polymorphism. The G allele of the rs671 was positively linked with alcohol intake. The ALDH2 rs671 genetically determined alcohol intake was not linked to the risk of psoriasis in the 2SLS analysis (β = −0.011, P = 0.960). The MR replication study also found no evidence of genetic propensity to greater alcohol consumption increasing the risk of psoriasis (β = −0.00065, P = 0.6002 in IVW; β = −0.00099, P = 0.6851 in MR-Egger; and β = −0.00181, P = 0.3558 in weighted median analysis). Conclusion: ALDH2 rs671 may not have a role in psoriasis susceptibility in Taiwanese. The MR analysis found no causality between alcohol consumption and psoriasis.

Analysis of selected genetic variants in psoriasis susceptibility and response to treatment.

Aetiology of psoriasis is complex with risk factors involving both environmental triggers and genetic background. Although the best characterized genetic risk factor for psoriasis is HLA-C*06 allele, a number of other variants were associated with the disease. In the current paper we have conducted a confirmation study for SNPs located in 9 gene regions in a case-control analysis of 507 psoriatic patients and 396 controls from the Polish population. Subsequently the impact of genetic variants on response to topical and NB-UVB therapy (reduction in the Psoriasis Area and Severity Index) was analysed. Significant differences in genotype and/or allelic frequency were observed for the following SNPs: rs33980500 (TRAF3IP2), rs582757 (TNFAIP3I), rs12188300 (IL12B), rs28998802 (NOS2), and rs2233278 (TNIP1). None of the genetic factors was associated with treatment outcome. Although the genetic variants have an impact on the disease risk, they are unlikely to be useful in personalization of topical therapy.

Association between the IL-6 polymorphisms and coal workers’ pneumoconiosis in a Chinese Hui population

ObjectiveTo determine whether polymorphisms in IL-6 and IL-12 contribute to the etiology of coal workers’ pneumoconiosis (CWP) in a Chinese Hui population, and to evaluate the efficacy and safety of high frequency oscillatory ventilation (HFOV) in the treatment of CWP.IntroductionGenes and the environments interplay in the development of CWP, and the association between the potential functional polymorphisms in many genes and CWP have been reported.MethodsWe genotyped the IL-6-634C/G (rs1800796) and IL-12B-1188A/C (rs3212227) polymorphisms in a case-control study including 160 CWP patients and 150 dust-exposed control subjects of Chinese Hui population, and analyzed the associations between these genetic variants and CWP risk. We also evaluated the efficacy and safety of HFOV for whole lung lavage (WLL) in the treatment of CWP.ResultsCarrying the C allele of IL-6-634C/G (rs1800796) was associated with decreased risk of CWP ( p &lt; 0.05). No significant differences in allele or genotype frequencies of IL-12B-1188A/C was found between the CWP cases and control subjects ( p &gt; 0.05). Compared with CWP patients with routine WLL, CWP patients received HFOV showed better pulmonary functions. HFOV treatment also yield a significant higher efficient rate (97.50%) than WLL treatment (81.25%, p = 0.001). CWP patients receiving HFOV and WLL treatment both showed significantly increased serum contents of Clara cell protein 16 (CC16) and superoxide dismutase (SOD), and decreased serum contents of serum malonaldehyde (MDA). While the increasing of CC16 and SOD, and decreasing of MDA in patients receiving HFOV was more noticeable than patients receiving WLL.ConclusionsTaking together, the −634C/G polymorphisms in IL-6 play a role in the etiology of CWP. HFOV, when applied in CWP patients, significant improves their pulmonary functions.

Associations of IL-6 polymorphisms with Behçet’s Disease in Denizli, province of Turkey

Behçet's Disease is a chronic, multisystemic disease and the etiopathogenesis of the disease develop as a result of the interaction of environmental and genetic factors. IL-6 is a proinflammatory cytokine with functions on immune response regulation and chronic inflammation demonstrated by increased serum levels and gene expression studies in Behçet’s disease. We genotyped IL-6; rs1800797, rs1800796 and rs1800795 polymorphisms in 78 patients with Behçet’s disease and 130 healthy controls using PCR-RFLP based approach. No statistically significant difference in allele or genotype frequencies of IL-6, rs1800797 and rs1800796 was found in between groups. We determined that in the BD patients with genital ulcers, arthritis and without vascular involvement was found to have significantly different IL-6, SNP frequencies compared with healthy controls. In addition, the IL-6 rs1800795 GC genotype and C allele may contribute to the development of the disease in female BD. The haplotype distributions of all loci of IL-6 were examined and GGG was found as the highest frequency haplotype in both groups. In conclusion, the results of our study showed that IL-6 rs1800795 may associate with the susceptibility to the BD. Studies should be conducted with more SNPs in large and different populations need to evaluate the contribution of responsible alleles for the disease and its clinical features.