Cytokine gene polymorphisms are known to be associated with functional differences in cytokine regulation and may affect host susceptibility to tuberculosis (TB). Contacts are important group in developing tuberculosis infection and are 10–60 times more likely to develop TB than general population. The present study was carried out in patients with TB (N = 176), their household contacts (HHC; N = 155) from Free Chest TB Clinic PPM DOTS (1TU) covering 500,000 population at Mahavir Hospital and Research Centre, Hyderabad, and healthy controls (HC; N = 170) also included. The association of single‐nucleotide polymorphisms (SNPs) in the promoter region of TNF‐α (−308G/A), IL‐2 (−330T/G), IL‐4 (−589C/T) and in exon region of TGF‐β1 (+869T/C) genes was assessed by ARMS & PCR‐RFLP using specific primers in the above‐mentioned subjects. The differences in allelic or genotypic frequencies of TNF‐α (−308G/A) between patients, their HHC and HC were not statistically significant (P > 0.05). IL‐2 (−330T/G) TG genotype was significantly different between patients, HHC compared to HC (P < 0.002, OR‐1.997, 95%CI‐1.260‐3.168, P < 0.03, OR‐1.602, 955CI‐1.003‐2.561).IL‐4 (−589C/T) CC genotype was significantly different between patients and HC (P < 0.03, OR‐1.791, 95%CI‐1.009‐3.189) as well as between HHC and HC at P < 0.0001, OR‐2.56, 95%CI‐1.448‐4.545. In addition, the TGF‐β 1 (+869T/C) TC genotype was significantly associated with susceptibility to tuberculosis in patients when compared against HC(P < 0.0001, OR‐3.416, 95%CI‐2.063‐5.670) and HHC (P < 0.0001, OR‐2.357, 95%CI‐1.439‐3.868), respectively.MDR analysis indicated that TT genotype of TGF‐β1 with TT and CT genotypes of IL‐4 showed high risk with GA, TT genotypes of TNF‐α, IL‐2, respectively. Our results suggest that IL‐2 (‐330T/G), IL‐4 (‐589 C/T) and TGF‐β1 (+869T/C) gene polymorphisms may be associated with TB susceptibility.
BackgroundIn India, despite well-established anti-retroviral treatment programs, Cytomegalovirus (CMV) infection-related end-organ diseases (EODs) still remain a major concern resulting in exacerbation of morbidity and mortality among HIV/AIDS patients. A prospective study was designed to understand the distribution and prognosis of CMV associated EODs and to determine a standardized cut-off value for serum CMV viral load associated with the development of EODs amongst HIV/AIDS subjects.MethodsIn a cohort of 400 late-diagnosed HAART naïve HIV/AIDS subjects attending anti-retroviral centers of Kolkata during 2008–2014, the median duration of follow-up was 560 days, and at least 3 visits subsequent to the baseline were mandatory for eligibility. HIV-1 and CMV viral load were estimated by performing Real-Time Polymerase Chain Reactions (PCR).ResultsAmong subjects, 40.5% (162/400) had CMV EODs which were more common at lower CD4 counts. Poor prognosis and higher death rate were associated with a low CD4 count and increased HIV-1 and CMV viral loads. Subjects having higher CD4 count responded better to therapy [for CD4 = 60–100: Risk Ratio:RR = 1.48 (95% Confidence Interval: 95%CI = 1.18–1.82) and for CD4 = 30–59: RR = 1.64 (95%CI = 1.18–2.27)]. The cut off value of the serum CMV viral load (expressed as log10DNA/ml serum) associated with the development of EODs and disseminated CMV EODs was determined as 5.4 (p<0.0001) and 6.4 (p<0.0001) respectively. These cut offs were found to have satisfactorily high sensitivity, specificity, positive and negative predictive values.ConclusionPrognosis of CMV EOD was poor as indicated by higher death rates among subjects with lower CD4 count, and specific cut-off values were found to have useful potential for identification and treatment of CMV infected HIV/AIDS patients in due time to avoid CMV EODs among HIV/AIDS subjects. Targeted intervention programs seemed to be required urgently to make these cut-offs operational in order to minimize the burden of CMV EOD in this vulnerable population.
Background Cytomegalovirus [CMV] is a causative agent of congenital infection worldwide and often leads to neurological deficits and hearing loss in newborns. Infants born with symptomatic congenital Cytomegalovirus infection [cCMV] are at significant high risk for developing adverse long-term outcomes. In this study, we look into the sequence variability of surface glycoprotein B [gB] encoding region in newborns with symptomatic CMV infection for the first time in Eastern region of India. Methods 576 suspected newborns from seropositive mothers were subjected to the study and ELISA was used to confirm CMV infection. Different genotypes and their subtypes were determined using multiplex nested-PCR. Viral load of different glycoprotein B [gB] genotypes was measured using RT-PCR. Sequencing and phylogenetic analysis was then performed using Bayesian interference. Results The overall frequency of cCMV infection was 18.4%, where 16.0% neonates were symptomatic. Among the different gB genotypes, gB1 had the highest frequency [23.5%] and gB4 showed the lowest occurrence [5.8%]. 23.5% of symptomatic neonates had mixed genotypes of gB, probably indicating matrenal reinfection with CMV strains in Indian population. Significant genotypic clades [gB1-gB2-gB3-gB5] were grouped closely based on gene sequences, but the gB4 sequence was in the outlier region of the phylogenetic tree indicating the genetic polymorphism. Conclusion This is the first study on cCMV genotyping and its phylogenetic analysis from Eastern Indian neonatal population. The study holds importance in the assessment of cCMV seroprevalence in global perspective. gB protein can be used as a potential therapeutic target against CMV infection.
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