scholarly journals IL-1RN and IL-1βPolymorphism and ARV-Associated Hepatotoxicity

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
HariOm Singh ◽  
Dharmesh Samani ◽  
Vijay Nema ◽  
Manisha V. Ghate ◽  
R. R. Gangakhedkar
Keyword(s):  
Hepatic Injury ◽  
Healthy Controls ◽  
Severe Hepatotoxicity ◽  
Pcr Rflp ◽  
Alcohol Users

The severity of hepatic injury depends upon cytokines. Previous studies associatedIL-1RNallele 2 withIL-1βproduction. Hence, we examined the association ofIL-1 RNandIL-1βpolymorphisms with ARV-associated hepatotoxicity. Genotyping ofIL-1RN(VNTR),IL-1β(-511C/T) polymorphisms was done in 162 HIV-infected patients, 34 with ARV hepatotoxicity, 128 without hepatotoxicity, and 152 healthy controls using PCR and PCR-RFLP method. The haplotypes 1T and 2C enhanced the risk for severe hepatotoxicity (OR=1.41,P=0.25;OR=1.67,P=0.31).IL-1β-511TT genotype significantly represented among tobacco using HIV-infected individuals compared to nonusers (OR=3.74,P=0.05).IL-1β-511TT genotype among alcohol users increased the risk for hepatotoxicity (OR=1.80,P=0.90).IL-1β-511CT and-511TT genotypes overrepresented in alcohol using HIV-infected individuals (OR=2.29,P=0.27;OR=2.64,P=0.19).IL-RN2/2 and 1/3 genotypes represented higher in nevirapine using hepatotoxicity patients (OR=1.42,P=0.64,OR=8.79,P=0.09).IL-1β-511CT and-511 TT genotypes among nevirapine users enhanced the risk for severe hepatotoxicity (OR=4.29,P=0.20;OR=1.95,P=0.56).IL-1β-511CT and-511TT genotypes were overrepresented in combined nevirapine and alcohol using HIV-infected individuals as compared to nevirapine users and alcohol nonusers (OR=2.56,P=0.26;OR=2.84,P=0.24).IL-1β-511TT genotype with tobacco, alcohol, and nevirapine usage revealed a trend of risk for the development of ARV-associated hepatotoxicity and its severity.

Occurrence of Interleukin-2 (330 G/T) Promoter Polymorphism in ARV associated hepatotoxicity

2019 ◽  
Vol 19 (3) ◽  
pp. 206-215
Author(s):  
HariOm Singh ◽  
Nayana Nambiar ◽  
Dharmesh Samani ◽  
Raman R. Gangakhedkar
Keyword(s):  
Hepatic Injury ◽  
Interleukin 2 ◽  
Promoter Polymorphism ◽  
Healthy Controls ◽  
Hiv Replication ◽  
Hiv Patients ◽  
Pcr Rflp

Background: IL-2 cytokine is involved in HIV replication and is also known to cause hepatic injury. Polymorphisms in the IL-2 gene are associated with altered interleukin-2 production. Methods: Hence, we assessed the prevalence of IL-2-303G/T polymorphism in 165 HIV patients (34 with and 131without hepatotoxicity) and 155 healthy controls using the PCR-RFLP method. Results: In patients with hepatotoxicity, IL-2-303GT, -303GT+TT genotypes were less prevalent as compared to without hepatotoxicity and healthy controls (29.4% vs. 42.7%, 58.8% vs. 69.5%; 29.4% vs. 40.6%, 58.8% vs. 66.5%, respectively). In patients with hepatotoxicity using tobacco and alcohol, IL-2-303GT,-303TT genotypes were distributed higher as compared to non-users (42.9% vs. 25.9%, OR=8.52, 42.9% vs. 25.9%, OR=9.09, and 28.6% vs. 29.6%, OR=1.63, 42.9% vs. 25.9%, OR=2.93), while IL-2-303TT genotype occurred more often in HIV patients consuming alcohol (34.1% vs. 23.0%). Nevirapine users with hepatotoxicity overrepresented the IL-2-303GT,-303TT genotypes as compared to efavirenz (34.8% vs. 18.2%, OR=4.64, 34.8% vs. 18.2%, OR=3.88). Among nevirapine users, IL-2-303GT genotype was associated with susceptibility to the acquisition of hepatotoxicity with borderline significance (OR=4.24, P=0.06). HIV patients using nevirapine majorly represented the IL-2-303TT genotype (26.9% vs. 25.0%, OR=2.35) while HIV patients with nevirapine + alcohol usage presented the IL-2 -330TT genotype at a higher frequency (34.2% vs. 23.5%, OR=1.51). In patients with hepatotoxicity using nevirapine + alcohol, the genotype IL-2 - 330TT was predominant (60.0% vs. 27.8%, OR=3.16). Conclusion: Thus, IL-2-303G/T polymorphism did not confer the susceptibility to ARV associated hepatotoxicity. However, IL-2-303G/T polymorphism with nevirapine usage may facilitate the risk for acquisition of ARV associated hepatotoxicity.

scholarly journals Tissue Inhibitor of Metalloproteinase-2 Polymorphisms and Risk for HIV-Associated Neurocognitive Disorder

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
HariOm Singh ◽  
Sushma Jadhav ◽  
Dharmesh Samani ◽  
Sumitra Nain
Keyword(s):  
Significant Risk ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Disease Stage ◽  
Neurocognitive Disorder ◽  
Healthy Controls ◽  
Hiv Disease ◽  
Hiv Patients ◽  
Pcr Rflp ◽  
And Gender ◽  
Alcohol Users

The imbalance between MMPs and TIMPs is associated with the HIV dissemination tissue damage pathology neurodegenerative disorders, including HAND. Genetic variations in the TIMP gene may modulate the neurocognitive disorder in HIV patients. Hence, we evaluated the genetic variants of TIMP-2 (-418G/C, 303G/A) gene with the risk of HAND. Genotyping of TIMP-2 polymorphism was performed in 50 patients with HAND, 100 no HAND, and 154 healthy controls by PCR-RFLP. TIMP-2 -418GC and 303AA genotypes represented a predominant risk for HAND severity (OR=1.55, P=0.30; OR=4.58, P=0.24). The variant -418CC genotype, -418A allele, had exhibited a significant risk for the acquisition of HAND (OR=12.55, P=0.026; OR=2.66, P=0.004). TIMP-2 303GA, 303AA genotype, and 303A allele evinced a higher risk for HAND severity (OR=1.82, P=0.14; OR=1.70, P=0.63; and OR=1.68, P=0.12). In HIV patients, TIMP-2 -418CC genotype and -418C allele significantly occurred in comparison to healthy controls (OR=10.10, P=0.006; OR=2.02, P=0.009). In the intermediate and early HIV disease stage, TIMP-2 -418CC genotype was significantly increased compared with healthy controls (11.1% vs. 1.3%, OR=14.63, P=0.01; 16.9% vs. 1.3%, OR=14.51, P=0.002). In patients with HAND among tobacco and alcohol users, TIMP-2 -418CC genotype displayed a risk for HAND severity (OR=3.96, P=0.26; OR=4.83, P=0.19). On multivariate logistic regression, TIMP-2 303AA genotype, advanced stage, and gender had a risk for HAND severity (OR=28.98, P=0.02; OR=2.35, P=0.070; and OR=2.36, P=0.04). In conclusion, TIMP-2 -418G/C polymorphism independently, along with alcohol and tobacco, may have an impact on the acquisition of HAND and its severity. TIMP-2 303G/A polymorphism bare a risk for HAND severity.

scholarly journals TLR7 Polymorphism (rs179008 and rs179009) in HIV-Infected Individual Naïve to ART

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
HariOm Singh ◽  
Dharmesh Samani ◽  
Sumit Aggarwal
Keyword(s):  
Infected Individual ◽  
Univariate Analysis ◽  
Disease Stage ◽  
Rapid Decline ◽  
Healthy Controls ◽  
Single Nucleotide ◽  
Codominant Model ◽  
Pcr Rflp ◽  
Hiv 1 ◽  
Cd4t Cell

Toll-like receptors (TLRs) play an important role in the innate immune response to HIV infection. Single nucleotide polymorphism (SNP) in TLR7 (Gln11Leu) gene has been associated with a rapid decline of CD4T cell count. Hence, we assessed the TLR7 (rs179008, Gln11Leu (A/T) and rs179009, IVS2-151 (A/G)) polymorphism in 150 HIV-infected individuals naïve to ART and 158 healthy controls. The genotyping of TLR7 Gln11Leu (A/T) and IVS2-151 (A/G) polymorphisms was done using the PCR-RFLP method. In univariate analysis, none of the genotype and haplotype of TLR7 Gln11Leu (A/T) and IVS2-151 (A/G) polymorphism differed significantly between HIV-infected individuals and healthy controls. The occurrence of TLR7 rs179009AG genotype in the codominant model and rs179009 AG-GG genotype in the dominant model was significantly reduced in HIV-infected individuals as compared to healthy controls (18.0% vs. 29.1%, OR=0.42, P=0.016; 26.7% vs. 36.7%, OR=0.52, P=0.016). TLR7 rs179009AG genotype was significantly underrepresented in the intermediate HIV disease stage compared with healthy controls (OR=0.03, P=0.04). TLR7 rs179009AG genotype expressed higher in tobacco-consuming HIV-infected individuals compared with nonusers (OR=1.71, P=0.47). In conclusion, rs179009 AG-GG and AG genotypes were found reduced in HIV-infected individuals as compared to healthy controls; their higher prevalence in health individuals clearly support that they are associated with reduced risk of acquisition of HIV-1 infection.

scholarly journals Rofecoxib-Induced Hepatotoxicity: A Forgotten Complication of the Coxibs

2006 ◽  
Vol 20 (5) ◽  
pp. 351-355 ◽  
Author(s):  
Brian Yan ◽  
Yvette Leung ◽  
Stefan J Urbanski ◽  
Robert P Myers
Keyword(s):  
Hepatic Injury ◽  
Hepatic Dysfunction ◽  
Cyclooxygenase 2 ◽  
Liver Histology ◽  
Cardiovascular Safety ◽  
Drug Induced ◽  
Severe Hepatotoxicity ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Rofecoxib is a member of the coxib family of nonsteroidal anti-inflammatory drugs that selectively inhibit cyclooxygenase-2. Although the coxibs are generally well-tolerated, rofecoxib was recently withdrawn from the market due to concerns regarding cardiovascular safety. Rare cases of hepatic injury attributable to the coxibs have been reported. In the present study, two additional cases of severe hepatotoxicity are described in patients with cholestatic symptoms and abnormal liver biochemistry, shortly following the initiation of rofecoxib for arthritic complaints. In both cases, liver histology was compatible with drug-induced hepatotoxicity, and rapid clinical and biochemical improvements were observed following rofecoxib discontinuation. With new coxibs and expanding indications on the horizon, physicians in all areas of practice must be aware of this disorder and consider it in any patient who develops hepatic dysfunction after taking a coxib.

scholarly journals A Family Screening of CD19 Gene Mutation by Restriction Fragment Length Polymorphism

2021 ◽  
Author(s):  
Mehmet Ali Karaselek ◽  
Hasan Kapaklı ◽  
Sukru Guner ◽  
Sevgi Keleş ◽  
Ismail Reisli
Keyword(s):  
B Lymphocyte ◽  
Index Case ◽  
Genetic Diagnosis ◽  
Newborn Baby ◽  
Fast Method ◽  
Healthy Controls ◽  
Heterozygous Genotype ◽  
First Case ◽  
Pcr Rflp ◽  
Homozygous Mutant

Background: CD19 molecule found on B lymphocyte surface forms CD19 complex together with CD21, CD81, CD225 in mature B cells and regulates B lymphocyte activation with antigen stimulation. Mutation(s) in the gene encoding the CD19 molecule affect CD19 protein expression and primary immunodeficiency (PID) occurs. Some genetic method, especially sanger and next generation sequencing and flow cytometric methods are widely used in the diagnosis of PID. The RFLP method, which is faster and cheaper than other mutation detection methods, is rarely used in the diagnosis of PID. The study aimed to genetically identify CD19 deficiency, which is a PID, using the RFLP method. Methods: The study was performed at Necmettin Erbakan University, Meram Medicine Faculty Hospital, Pediatric Allergy and Immunology clinic. A total of 8 patients and two healthy controls could be included in the study. A total of 8 patients and two healthy controls were included in the study, and the relevant region genotypes in the CD19 gene were determined by performing RCR-RFLP analysis. Results: CD19 deficiency was first described by us. The index case, newborn baby and mother were also included in the study. It was determined that the index case (P6) was homozygous mutant, the newborn baby (P7) and mother (P8) had heterozygous genotype. Based on this situation, one child (P1) was found to be homozygous mutant, mother (P2), father (P3) and other children (P4 and P5) had heterozygous genotype in the family, which was determined to be related to the first case. Conclusion: Rapid genetic diagnosis in patients suspected of having a known case of PID insufficiency as a result of clinical and laboratory findings carries a vital risk in terms of treatment options to be offered to patients. Although PCR-RFLP, which is a cheap, safe and fast method, is used to detect known mutations, the use of PID is rare. In our study, it has been shown that it is a method that can be used in the diagnosis of PID by determining genotypes using PCR-RFLP, and especially in terms of rapid genetic testing of family screenings.

scholarly journals ATM polymorphisms IVS24-9delT, IVS38-8T>C, and 5557G>A in Mexican women with familial and/or early-onset breast cancer

2014 ◽  
Vol 56 (2) ◽  
pp. 206 ◽  
Author(s):  
Fabiola Del Carmen Calderón-Zúñiga ◽  
Guadalupe Ocampo-Gómez ◽  
Francisco Carlos López-Márquez ◽  
Rogelio Recio-Vega ◽  
Luis Benjamín Serrano-Gallardo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Onset ◽  
Mexican Population ◽  
Mexican Women ◽  
Healthy Controls ◽  
Test Results ◽  
Early Onset Breast Cancer ◽  
Pcr Rflp ◽  
Chilean Population ◽  
Mexican Populations

 Objective. To assess whether in Mexican population the frequencies of ATM polymorphisms IVS24-9delT, IVS38-8­T>C, and 5557G>A in breast cancer (BC) cases and healthy controls were different from those found in other countries. Materials and methods. Frequencies of polymorphisms conferring BC risk IVS24-9delT, IVS38-8T>C, and 5557G>A were analyzed by PCR-RFLP in 94 patients with familial and/or early onset BC, and 97 healthy controls randomly selected. Allele frequencies analysis was done using χ2 and Hardy-Weinberg test. Results. Frequencies of heterozygous were: for 5557G>A, 13% cases, 0%controls (p=0.0009); for IVS24-9delT, 21% cases, 8% controls (p=0.0122); for IVS38-8T>C, only one case. 5557G>A and IVS24-9delT were more frequent in cases than in controls. The allelic frequen­cies found in 5557G>A are similar to those described by González-Hormazábal in Chile. Conclusion. The similarity of results in this polymorphism between Chilean and Mexican populations may be due to both being crossbred with an Amerindian-Spanish component, while differences may be due to fact that Chilean population has a greater European component than Mexican’s.

scholarly journals Correlations of PD-1/PD-L1 Gene Polymorphisms with Susceptibility and Prognosis in Non-Hodgkin lymphoma in Iranian Population

2020 ◽  
Author(s):  
hosnie hoseini ◽  
Parichehreh Yaghmaei ◽  
Gholamreza Bahari ◽  
saeed aminzadeh
Keyword(s):  
Hodgkin Lymphoma ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Non Hodgkin Lymphoma ◽  
Increased Risk ◽  
Pcr Rflp ◽  
Prognosis Marker ◽  
Pcr Method ◽  
Programed Cell Death ◽  
The Relationship

Abstract Background, Programed cell death 1 (PD-1) and its ligand (PD-L1) activity have already detected in various cancers. In non-Hodgkin lymphoma (NHL), however, the prognostic value of PD-1/PD-L1 genes polymorphisms and expression levels remains unclear. In the present study we aimed to investigate the relationship between genetic polymorphisms of PD-1/PD-L1 genes and non-Hodgkin lymphoma in Iranian papulation. Methods , four single nucleotide polymorphisms of the PD-1/PD-L1 genes, including 134 NHL patients and 125 healthy controls were examined using PCR-RFLP method. The expression level of PD-1/PD-L1 genes were analyzed using real time PCR method. Results , our data demonstrated that the PD-L1 rs2890685 (A>C) SNP (p<0.0001) significantly was associated with increased risk of NHL. The AA genotype of PD-L1 rs2890685 polymorphism was found to be more prevalent in NHL patents compared to healthy controls. No significant association were found between PD-L1 rs4143815, PD-1 rs11568821, PD-1rs2227981 SNPs and the risk of NHL incidence. Furthermore, our data showed that the mRNA transcription levels of both PD-1 and PD-L1 were significantly higher than normal healthy controls (p<0.001). Conclusion , Collectively, our finding demonstrated that the functional PD-L1 rs2890685 polymorphism was associated with NHL risk, suggesting that genetic variant of PD-L1 might be a possible prognosis marker for prediction of NHL risk and its development.

scholarly journals Does i-T744C P2Y12 Polymorphism Modulate Clopidogrel Response among Moroccan Acute Coronary Syndromes Patients?

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Hind Hassani Idrissi ◽  
Wiam Hmimech ◽  
Nada El Khorb ◽  
Hafid Akoudad ◽  
Rachida Habbal ◽  
...  
Keyword(s):  
Acute Coronary Syndromes ◽  
Interindividual Variability ◽  
Potential Effect ◽  
Healthy Controls ◽  
Wild Type ◽  
Pcr Rflp ◽  
Verifynow Assay ◽  
Coronary Syndromes ◽  
Development Risk ◽  
Transmission Models

Background. An interindividual variability in response to Clopidogrel has been widely described in patients with acute coronary syndromes (ACS). The contribution of genetics on modulating this response was widely discussed. The objective of our study was to investigate the potential effect of i-T744C P2Y12 polymorphism on Clopidogrel response in a sample of Moroccan ACS patients. We tried also to determine the frequency of this polymorphism among Moroccan ACS compared to healthy subjects. Methods and Results. 77 ACS patients versus 101 healthy controls were recruited. DNA samples were genotyped by PCR-RFLP method. The VerifyNow assay was used to evaluate platelet function among ACS patients. Our results show that the mutant allele C was more frequent among ACS ST (+) than ST (−) patients (39% versus 19.8%, resp.), when the wild-type allele was more represented in the ACS ST (−) group (80.2%). The C allele frequency was higher among resistant than nonresistant patients (30% versus 20.8%, resp.). Comparison of ACS patients and healthy controls shows higher frequency of mutant C allele among cases compared to controls (22.73% versus 19.31%, resp.); there was a statistically significant association of the recessive and additive transmission models with the ACS development risk (OR [95% CI] = 1.78 [1.58–5.05], P=0.01 and OR [95% CI] = 1.23 [0.74–2.03], P<0.001, resp.), increasing thus the association of this polymorphism with the pathology. Conclusion. Our results suggest that this polymorphism may have a potential effect on Clopidogrel response among our Moroccan ACS patients and also on ACS development.

HLA-DRB1*15:01 and multiple sclerosis: a female association?

2011 ◽  
Vol 18 (5) ◽  
pp. 569-577 ◽  
Author(s):  
Haritz Irizar ◽  
Maider Muñoz-Culla ◽  
Olaia Zuriarrain ◽  
Estibaliz Goyenechea ◽  
Tamara Castillo-Triviño ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Molecular Basis ◽  
Association Studies ◽  
Ethnic Origin ◽  
Gene Variants ◽  
Healthy Controls ◽  
Vdr Gene ◽  
Pcr Rflp ◽  
Female Specific

Background: The association between multiple sclerosis (MS) and the HLA-DRB1*15:01 haplotype has been proven to be strong, but its molecular basis remains unclear. Vitamin D receptor (VDR) gene variants and sex have been proposed to modulate this association. Objectives: 1) Test the association of MS with *15:01 and VDR variants; 2) check whether VDR variants and/or sex modulate the risk conferred by *15:01; 3) study whether *15:01, VDR variants and/or sex affect HLA II gene expression. Methods: Peripheral blood from 364 MS patients and 513 healthy controls was obtained and DNA and total RNA were extracted from leukocytes. HLA-DRB1, DRB5 and DQA1 gene expression measurements and *15:01 genotyping were performed by qPCR. VDR variants were genotyped by PCR-RFLP. Results: Our data confirms that the *15:01 haplotype confers a higher risk of suffering from MS (OR = 1.364; 95% CI = 1.107–1.681). No association was found between VDR variants and MS, but they were shown to moderately modulate the risk conferred by *15:01. Sex confers a much stronger modulation and the *15:01-MS association seems to be female specific. A higher *15:01 frequency has been observed in Basques (45.1%). *15:01 positive samples showed a significant overexpression of DRB1 ( p < 0.001), DRB5 ( p < 0.001) and DQA1 ( p = 0.004) in patients. DRB1 ( p = 0.004) and DRB5 ( p < 0.001) were also overexpressed in *15:01 controls. Conclusions: We confirm the *15:01-MS association and support that it is female specific. The relevance of ethnic origin on association studies has also been highlighted. HLA-DRB1*15:01 seems to be a haplotype consistently linked to high HLA II gene expression.

Role of MMP-2 and its inhibitor TIMP-2 as biomarkers for susceptibility to systemic lupus erythematosus

2020 ◽  
Vol 14 (12) ◽  
pp. 1109-1119
Author(s):  
Hemant J Vira ◽  
Vandana D Pradhan ◽  
Vinod D Umare ◽  
Ajay K Chaudhary ◽  
Anjali G Rajadhyksha ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Serum Level ◽  
Mrna Expression ◽  
Lupus Erythematosus ◽  
Serum Levels ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Functional Polymorphisms ◽  
Pcr Rflp

Aim: To investigate the possible association between MMP-2 (−1575 G/A, −1306 C/T) and its inhibitor TIMP-2 (−418 G/C) functional polymorphisms with development of severity in systemic lupus erythematosus (SLE) patients. Materials & methods: 150 SLE patients and matched healthy controls were recruited. Polymorphisms were detected by PCR-RFLP and serum levels by ELISA. Results: Mean MMP-2 and TIMP-2 serum level and mRNA expression were significantly increased in SLE cases as compared with controls (p < 0.0001). The concomitant presence of both MMP-2 1575A and its inhibitor TIMP-2 418C alleles synergistically increased the risk of SLE by 3.25-fold (CI: 1.44–7.34, p = 0.003). Conclusion: MMP-2, TIMP-2 and MMP-2/TIMP-2 ratios may act as biomarkers for susceptibility to SLE.

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