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Highlights: [•] First attempt from north India to dissect IL-17 axis in human tuberculosis (TB). [•] No association of IL17A and IL17F gene variants in pulmonary and extra-pulmonary TB [•] Correlated the serum cytokine levels and genotypes [•] IL17 variants might not be a major influencing gene for tuberculosis in north Indians. [ABSTRACT FROM AUTHOR]

Abstract: Globally only 5–10% of people encountering Mycobacterium tuberculosis have a lifetime risk of active disease indicating a strong host genetic bias towards development of tuberculosis. In the current study we investigated genotype variants pertaining to five cytokine genes namely IFNG, TNFA, IL4, IL10 and IL12 in the north Indian population with active pulmonary tuberculosis (APTB) and correlated the serum cytokine levels with the corresponding genotypes. Twenty five single nucleotide polymorphisms (SNPs) including six loci examined for the first time in tuberculosis were selected for genotyping in 108 patients with APTB from north India and 48 healthy regional controls (HC). Applying exclusion criteria 12 SNPs passed all the filters and were analysed further. The serum cytokine concentrations were measured by ELISA. Compared to HC mean serum IFN-γ, IL-12, IL-4, and IL-10 levels were higher in APTB (p =0.3661, p =0.0186, p =0.003, p =0.7, respectively). In contrast the mean serum TNF-α level was higher in HC (p =0.007). Comparison of genotypes and serum levels of the corresponding cytokine genes reveal that though IFN-γ and IL-4 levels were higher in APTB the genotype variants showed no difference between HC and APTB. In contrast the genotypes of the selected rsIDs in the TNFA, IL12 and IL10 genes showed significant association with the varying serum levels of corresponding cytokines. The variant of the TNFA gene at rs3093662, the IL12 gene at rs3213094 and rs3212220 and the IL10 gene at rs3024498 did show a strong indication to be of relevance to the immunity to tuberculosis. To our knowledge this is the first report from this region relating genotypes and serum cytokine levels in north Indian population. [Copyright &y& Elsevier]

Aim of Study: Endothelial dysfunction is a feature of cardiovascular disease, hypertension, dyslipidaemia and smoking, all of which are associated with diabetes induced nephropathy. The Cytokines have also found to play an important role in development of Diabetic nephropathy. Cytokines like monocyte chemoattractant protein-1 (MCP-1), and regulated upon activation and normal T cell expressed and secreted (RANTES) and their receptors CCR2 and CCR5 mediate macrophage infiltration into kidney whose over-expression leads to glomerulosclerosis and interstitial fibrosis. We investigated the association of three single nucleotide polymorphisms (SNPs) and three insertion deletion polymorphisms from CCR5, MCP-1 and endothelial nitric oxide synthase (eNOS) genes among 400 type 2 diabetic individuals with (DNP) and without nephropathy (DMT2). Materials and Methods: Genotyping of the Insertion/Deletion polymorphisms was performed by PCR whereas the SNPs were genotyped by the PCR-RFLP assay, followed by agarose gel electrophoresis. The serum nitric oxide and hs-CRP levels were also assessed. Results: The prevalence of the MCP-1 I/I (AGCTCCTCCTTCTC/AGCTCCTCCTTCTC) homozygotes was significantly higher among DNP than among DMT2 group (P<0.0001, OR: 2.19, 95% CI: 1.4-3.2), however frequency of both the alleles of MCP-1-2518 A> G promoter polymorphism did not vary significantly between the two groups. The frequency of D allele (CCR5 delta I/D) and DD genotype was significantly higher in DNP than among DMT2 patients (D allele: P=0.001, OR: 2.59, 95% CI: 1.4-4.6; DD genotype: P<0.0001, OR: 3.1, 95% CI: 2.1-4.6). The variant genotype (CO, II, and TT) frequencies of all the three eNOS polymorphisms (-786 T>C, Intron 4 I/D, and 1917 G > T) differed significantly (P< 0.05) between the two groups. The hsCRP levels were higher in DNP (2.15±2.0 mg/L; P<0.05) as compared to DMT2 group (1.89±1.7 mg/L; P<0.05), but were statistically non-significant. The NO levels of DNP group (0.4±0.04 nmol/L) were significantly lower as compared to DMT2 group (0.75±0.18 nmol/L). Conclusion: Although hs-CRP levels were increased in diabetic patients, no direct association of the increased hs-CRP levels was observed with DNE Also, this study reveals an association of CCR5 delta (32 bp I/D), and MCP-1 gene I/D, eNOS -786 T> C promoter, Intron 4 I/D and 1917 G>T polymorphisms, but not MCP-1 gene promoter polymorphism (-2518 A>G) with the development of type 2 DNP among North Indians. [ABSTRACT FROM AUTHOR]