title: Genetic variation in Micro-RNA genes of host genome affects clinical manifestation of symptomatic Human Cytomegalovirus infection.
abstract: BACKGROUND
  Micro-RNAs are implicated in various physiological and pathologic processes. In this study, we tested whether Micro-RNA gene variants of host-genome affect clinical manifestation of symptomatic HCMV infection.
  
  
  METHODS
  HCMV infection was detected by fluorescent PCR and immuno-histochemistry. The detection of genetic variants of four studied Micro-RNA tag-SNPs was done through PCR-RFLP assay and validated with DNA sequencing.
  
  
  RESULTS
  We observed an increased risk ranged from 3-folds to 5-folds among symptomatic HCMV cases for mutant genotype of rs2910164 (crude OR=3.11, p=0.009 and adjusted OR=3.25, p=0.007), rs11614913 (crude OR=3.20, p=0.006 and adjusted OR=3.48, p=0.004) and rs3746444 (crude OR=4.91, p=0.002 and adjusted OR=5.28, p=0.002) tag-SNPs. Interestingly, all the tag-SNPs that were significant after multiple comparisons at a FDR of 5% in symptomatic HCMV cases remained significant even after bootstrap analysis, providing internal validation to these results. Multifactor Dimensionality Reduction (MDR) analysis revealed 5-folds increased risk for symptomatic HCMV cases under the four-factor model (rs2910164, rs2292832, rs11614913 and rs3746444).
  
  
  CONCLUSIONS
  These results suggest that Micro-RNA gene variants of host-genome may affect clinical manifestation of symptomatic HCMV infection.
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, UP, India; Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, UP, India.
authors.forename: Maneesh Kumar
authors.initials: MK
authors.lastname: Misra
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, UP, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Department of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, UP, India.
authors.forename: Shashi Kant
authors.initials: SK
authors.lastname: Pandey
authors.affiliation: Department of Urology and Renal Transplantation, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, UP, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kapoor
authors.affiliation: Department of Nephrology, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, UP, India.
authors.forename: Raj Kumar
authors.initials: RK
authors.lastname: Sharma
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post-graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, UP, India. Electronic address: sur_ksha_agrawal@yahoo.co.in.
authors.forename: Suraksha
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D058070:Asymptomatic Diseases; D002908:Chronic Disease; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000472:pathogenicity / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D054884:Host-Pathogen Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D058011:Multifactor Dimensionality Reduction; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D035683:MicroRNAs
keywords: Cytomegalovirus infections; Genetic variation; HCMV; Host–pathogen interactions; MicroRNAs