Polymorphisms in the C-type lectin genes cluster in chromosome 19 and predisposition to severe acute respiratory syndrome coronavirus (SARS-CoV) infection

J Med Genet. 2008 Nov;45(11):752-8. doi: 10.1136/jmg.2008.058966. Epub 2008 Aug 12.

Abstract

Background: Polymorphisms of CLEC4M have been associated with predisposition for infection by the severe acute respiratory syndrome coronavirus (SARS-CoV). DC-SIGNR, a C-type lectin encoded by CLEC4M, is a receptor for the virus. A variable number tandem repeat (VNTR) polymorphism in its neck region was recently associated with susceptibility to SARS infection. However, this association was controversial and was not supported by subsequent studies. Two explanations may account for this discrepancy: (1) there may be an unknown predisposition polymorphism located in the proximity which is linked to the VNTR; or (2) it was a spurious association due to unrecognised population structure in the VNTR.

Methods: We performed a comprehensively genetic association study on this C-type lectin gene cluster (FCER2, CLEC4G, CD209, and CLEC4M) at 19p13.3 by a tagging single nucleotide polymorphisms (SNPs) approach.

Results: 23 tagSNPs were genotyped in 181 SARS patients and 172 population controls. No significant association with disease predisposition was detected. Genetic variations in this cluster also did not predict disease prognosis. However, we detected a population stratification of the VNTR alleles in a sample of 1145 Han Chinese collected from different parts of China.

Conclusion: The results indicated that the genetic predisposition allele was not found in this lectin gene cluster and population stratification might cause the previous positive association.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecules / genetics
  • China / epidemiology
  • China / ethnology
  • Chromosomes, Human, Pair 19 / genetics*
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Lectins, C-Type / genetics*
  • Minisatellite Repeats / genetics
  • Multigene Family*
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Cell Surface / genetics
  • Severe Acute Respiratory Syndrome / epidemiology
  • Severe Acute Respiratory Syndrome / ethnology
  • Severe Acute Respiratory Syndrome / genetics*
  • Severe acute respiratory syndrome-related coronavirus / pathogenicity*
  • Young Adult

Substances

  • CLEC4G protein, human
  • CLEC4M protein, human
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Receptors, Cell Surface