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A multifaceted computational report on the variants effect on KIR2DL3 and IFNL3 candidate gene in HCV clearance

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Abstract

HCV infection causes acute and chronic liver diseases including, cirrhosis and hepatocellular carcinoma. Following HCV infection, spontaneous clearance occurs in approximately 20 % of the population dependant upon HCV genotype. In this study, functional and non-functional variant analysis was executed for the classical and the latest HCV clearance candidate genes namely, KIR2DL3 and IFNL3. Initially, the functional effects of non-synonymous SNPs were assigned on exposing to homology based tools, SIFT, PolyPhen-2 and PROVEAN. Further, UTR and splice sites variants were scanned for the gene expression and regulation changes. Subsequently, the haplotype and CNV were also identified. The mutation H77Y of KIR2DL3 and R157Q, H156Y, S63L, R157W, F179V, H128R, T101M, R180C, and F176I of IFNL3 results in conservation, RMSD, total energy, stability, and secondary structures revealed a negative impact on the structural fitness. UTRscan and the splice site result indicate functional change, which may affect gene regulation and expression. The graphical display of selected population shows alleles like rs270779, rs2296370, rs10423751, rs12982559, rs9797797, and rs35987710 of KIR2DL3 and rs12972991, rs12980275, rs4803217, rs8109886, and rs8099917 of IFNL3 are in high LD with a measure of \({\text{r}}^{2 }\ge 0.8\) broadcasting its protective effect in HCV clearance. Similarly, CNV report suggests major DNA fragment loss that could have a profound impact on the gene expression affecting the overall phenotype. This roundup report specifies the effect of NK cell receptor, KIR2DL3 and IFNL3 variants that can have a better prospect in GWAS and immunogenetic studies leading to better understanding of HCV clearance and progression.

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Abbreviations

CNV:

Copy number variation

DAA:

Direct acting antiviral

DNA:

Deoxyribonucleic acid

GWAS:

Genome-Wide Association Study

HCV:

Hepatitis C virus

HLA-C :

Human leukocyte antigen-C

IFNL3 :

Interferon lambda 3

IL28B :

Interleukin 28B

KIR :

Killer immunoglobulin-like receptor gene

LD:

Linkage disequilibrium

NK:

Natural killer cells

RMSD:

Root mean square deviation

SNP:

Single nucleotide polymorphism

UTR:

Untranslated region

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Acknowledgments

The authors thank VIT University for their computational support in carrying out this work.

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  1. Bioinformatics Division, School of Biosciences and Technology, VIT University, Vellore, Tamil Nadu, 632014, India

    Pratichi Singh & J. Febin Prabhu Dass

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Correspondence to J. Febin Prabhu Dass.

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Singh, P., Dass, J.F.P. A multifaceted computational report on the variants effect on KIR2DL3 and IFNL3 candidate gene in HCV clearance. Mol Biol Rep 43, 1101–1117 (2016). https://doi.org/10.1007/s11033-016-4044-5

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