Genetic polymorphism in CD14 gene, a co-receptor of TLR4 associated with non-alcoholic fatty liver disease

AIM To evaluate the pathogenic role of toll-like receptor(TLR) gene polymorphisms in patients with nonalcoholic fatty liver disease(NAFLD).METHODS Two hundred and fifty subjects(NAFLD = 200, healthy volunteers = 50) underwent polymerase chain reaction and restriction fragment length polymorphism to assess one polymorphism in the toll-like receptor 2(TLR2) gene(A753G), two polymorphisms in the TLR4 gene(TLR4 Asp299 Gly and Thr399 Ile allele), and two polymorphisms in the cluster of differentiation 14(CD14)(C-159 T and C-550T) gene, a co-receptor of TLR4. Association of TLR gene polymorphisms with NAFLD and its severity was evaluated by genetic models of association.RESULTS On both multiplicative and recessive models of gene polymorphism association, there was significant association of CD14 C(-159) T polymorphism with NAFLD; patients with TT genotype had a 2.6 fold increased risk of developing NAFLD in comparison to CC genotype. There was no association of TLR2 Arg753 Gln, TLR4 Asp299 Gly, Thr399 Ile, and CD14 C(-550) T polymorphisms with NAFLD. None of the TLR gene polymorphisms had an association with histological severity of NAFLD.CONCLUSION Patients with CD14 C(-159) T gene polymorphism, a co-receptor of TLR4, have an increased risk of NAFLD development.

The incidence of sporadic viral hepatitis in North India:a preliminary study

BACKGROUND: Viral hepatitis is one of the major causes of mortality and morbidity in developing countries. Hepatitis E virus (HEV) among the major etiological agents is responsible for both sporadic and epidemic outbreaks. The epidemic outbreak is water-borne whereas the sporadic outbreak is possibly through contact. Various diagnostic tools at times fail to pinpoint the cause of viral hepatitis. This study was carried out to evaluate the utility of ELISA and nRT-PCR (nested reverse transcriptase polymerase chain reaction) for the diagnosis of sporadic and acute viral hepatitis (AVH) caused by HEV in an endemic situation in North India. METHODS: Serum samples were collected from all the affected and suspected persons and subjected to serological detection of HAV IgM, HBsAg, HCV antibody and HEV IgM. The samples that were positive for HEV IgM were further processed for the detection of HEV RNA by nRT-PCR. RESULTS: A total of 843 samples were collected from 685 patients with AVH, 70 patients with fulminant hepatic failure (FHF), 53 patients with chronic liver disease (CLD), 11 patients with antituberculosis therapy (ATT)-induced jaundice, and 24 pregnant women. The percentage of positivity for anti-HEV IgM was 58.3% in the pregnant women, 41.4% in the paients with FHF, 38.6% in the patients with AVH, 9.4% in the patients with CLD and 18.2% in the patients with ATT induced jaundice. 9.4% of HBsAg carriers were positive for anti-HEV IgM. Males outnumbered females (62.8% vs. 37.1%). Furthermore, the rates of fulminant and acute outbreaks of hepatitis with HEV RNA positivity were 41.4% and 9.4%, respectively. CONCLUSION: Serological and molecular analysis should be combined for the diagnosis of viral infections, especially in endemic areas.

Anti-endothelial cell antibody rich sera from rheumatic heart disease patients induces proinflammatory phenotype and methylation alteration in endothelial cells

Rheumatic heart disease(RHD)is a major cause of cardiovascular morbidity and mortality in developing nations like India.RHD commonly affects the mitral valve which is lined by a single layer of endothelial cells(ECs).The role of ECs in mitral valve damage during RHD is not well elucidated.In here,anti-endothelial cell antibody from RHD patients has been used to stimulate the ECs(HUVECs and HMVECs).ECs proinflammatory phenotype with increased expression of TNFa,IL-6,IL-8,IFNg,IL-1b,ICAM1,VCAM1,E-selectin,laminin B,and vimentin was documented in both ECs.The promoter hypomethylation of various key inflammatory cytokines(TNFa,IL-6,and IL-8),integrin(ICAM1)associated with leukocyte transendothelial migration,and extracellular matrix genes(vimentin,and laminin)were also observed.Further,the in-vitro data was in accordance with ex-vivo observations which correlated significantly with the etiological factors such as smoking,socioeconomic status,and housing.Thus,the study sheds light on the role of ECs in RHD which is a step forward in the elucidation of disease pathogenesis.