C21orf91 Genotypes Correlate With Herpes Simplex Labialis (Cold Sore) Frequency: Description of a Cold Sore Susceptibility Gene

• Published in: The Journal of infectious diseases 2011-12, Vol.204 (11), p.1654-1662
• Main Authors: Kriesel, John D., Jones, Brandt B., Matsunami, Nori, Patel, Milan K., St. Pierre, Christine A., Kurt-Jones, Evelyn A., Finberg, Robert W., Leppert, Mark, Hobbs, Maurine R.
• Format: Article
• Language: English
• Subjects: Antibodies, Viral - blood; Biological and medical sciences; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 21; Fundamental and applied biological sciences. Psychology; Genes; Genetic Association Studies; Genetic Linkage; Genetic Predisposition to Disease; Genotypes; Haplotypes; Herpes labialis; Herpes Labialis - genetics; Herpes Labialis - virology; Herpes simplex virus 1; Herpesvirus 1, Human - immunology; Human herpesvirus 1; Humans; Infectious diseases; Lod score; Major and Brief Reports; Market disequilibrium; Medical sciences; Microbiology; Phenotype; Phenotypes; Polymorphism, Single Nucleotide; Untranslated regions; VIRUSES
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jir633

Background. Herpes simplex virus type 1 (HSV-1) infects > 70% of the United States population. We identified a 3-megabase region on human chromosome 21 containing 6 candidate genes associated with herpes simplex labialis (HSL, "cold sores"). Methods. We conducted single nucleotide polymorphism (SNP) scans of the chromosome 21 region to define which of 6 possible candidate genes were associated with cold sore frequency. We obtained the annual HSL frequency for 355 HSV-1 seropositive individuals and determined the individual genotypes by SNPlex for linkage analysis and parental transmission disequilibrium testing (ParenTDT). Results. Two-point linkage analysis showed positive linkage between cold sore frequency and 2 SNPs within the C21orf91 region, 1 of which is nonsynonymous. ParenTDT analysis revealed a strong association between another C21orf9l SNP, predicted to lie in the 3' untranslated region, and frequent HSL (P = .0047). C21orf 91 is a predicted open reading frame of unknown function that encodes a cytosolic protein. Conclusions. We evaluated candidate genes in the cold sore susceptibility region using fine mapping with 45 SNP markers. 2 complementary techniques identified C21orf91 as a gene of interest for susceptibility to HSL. We propose that C21orf91 be designated the Cold Sore Susceptibility Gene-1 (CSSG1).