CLEC4E SNPS rs10841845 is located within untranslated region (3’UTR), although 3UTR may not influence direct translation mechanism nevertheless have regions that regulate addition of adenine tails to mRNA, translation efficiency and stability of the mRNA. The 3UTR has silencer regions which bind to repressor protein and inhibits the expression of mRNA and possess the binding sites for microRNA which inhibits translation or directly causing the degradation of the transcript affecting the gene expression18. In addition 3UTR dictates the addition of adenine residuals to form poly tail A for mRNA transcript therefore polymorphism in 3UTR of a gene affects its expression and protein function. rs10841847 is found in the intron region which considered as noncoding region.
Although gene polymorphisms in the intron region do not change amino acids coded, may influence the splicing, transcription process and gene expression19Various animal studies have investigated the response to immune system through mincle receptors to certain pathogenic ligands. Mincle receptors respond to Klebsiella pneumonie, this was demonstrated by an experiment, were exposed mincle deficient mice suffered a high bacterial load compared to mincle +/+ mice.20.It was confirmed that mincle recognises glucosyl diacylglycerol a carbohydrate lipid of streptococcus pneumonia as was demonstrated mincle -/- mice when exposed suffered a high bacterial load compared to mincle +/+ mice, and alveolar neutrophils from pneumococcal individuals had high mincle expression compared to those from general circulation21.it was found that corneal epithelial cells exhibited increased expression of mincle receptors in response to fungus22.mincle recognition of TDM accelerates granuloma formation and bacterial clearance;, Lee et al23demonstrated mincle knocked out(KO) mice suffered high bacterial load with no granuloma formation compared to wild type.
Clec4e as a gene has been linked to a number of inflammatory diseases and skin allergies 24, 25 and enables production of pro-inflammatory IL-1? 26.mincle deficient macrophage deficiently responds to BCG27, and production of granulocyte colony stimulating factor and tissue necrosis factor greatly compromised in mincle deficient mice10 In the present study we investigated the association of CLEC4E gene variants and susceptibility to PTB. The results from our study show that variations in the human gene CLEC4E encoding for mincle receptor have a strong significant difference between patients with pulmonary tuberculosis and healthy controls in Chinese Han population. mostly in genetic research the power of a sample set to detect an association mainly depends on alleles frequency and the size of its effect28.The frequency of rs10841845G and rs10841847A alleles in control group were significantly higher than those in case group. Thus meaning gene polymorphism increases the receptor capability to recognise ligands and transduces signals for effective immune response According to overall results genotypes and alleles at rs10841845 and rs10841847 were associated with increased protection against pulmonary tuberculosis, This did not coincide with the previous study findings on south African population as it was reported by Bowrker et al were no association observed for all SNPs17 this discrepancy could be due to difference in genetic factors and ethnicity of the study populations. In contrast to our findings also, Wu et al29 overall results rs10841845 had no significant association with rheumatoid arthritis in Chinese population. though its allele G in males under stratification is beneficial to the host resistance to rheumatoid arthritis 29 this correlation is based on genetics.
Incident rates of tuberculosis in most countries are more prevalent in males than female due sex specific factors of TB including sex steroid hormones that mediates the immune response and genomic polymorphism30 but our study results refuted this where by all SNPs genotypes and alleles were protective to all. Considering the synergic effect of SNPs on gene expression and function, The haplotype analysis of SNPs revealed that 2GA greatly confer increased risk to PTB since alteration reduces the receptor ability to recognise and transduce effective signals as compared to AA and GG haplotypes that have protective effect against developing PTB by positively influencing the cytokine production and naïve CD4+ cell differentiation thereafter affecting phagocytic cell process. SHEsisPlus software was used. (http://shesisplus.
biox.cn/SHEsis.html#).The value of D 0.81 indicated a linkage disequilibrium with the 2 SNPs co-inherited at around 81%, the r2 0.
14 was low due to allele frequency from recombination thus sufficient variation that can be analysed to distinguish between disease potential predisposing genetic variant. Figure1 ;2Nutrition has been identified as a factor that affects susceptibility to many infectious diseases. Tuberculosis can lead to malnutrition, and malnutrition lowers the immune system leading to increased likelihood to develop the active TB infection. Lipids such cholesterol forms the main cell membrane component maintaining the cell integrity and fluidity to enable execution of its function. Considering the normal cholesterol level (
