Polymorphisms of the ACE2 and CD13 (ANPEP) genes, and susceptibility to SARS coronavirus infection in Chinese from Hong Kong

Abstract

Angiotensin-converting enzyme 2 (ACE2), mapped on Xp22, has been recently found to be a receptor for the coronavirus causing severe acute respiratory syndrome (SARS-CoV). CD13 (ANPEP), alanyl (membrane) aminopeptidase mapped on 15q25-q26, is also a receptor for a number of coronaviruses. We investigated whether genetic polymorphisms of ACE2 and ANPEP might be associated with the susceptibility SARS-CoV infection in Chinese in Hong Kong. DNA extracted from 215 (female:127, male:88) SARS-CoV patients confirmed by either serology or RT-PCR assay, 177 (female:142, male:35) unaffected health care workers (HCW), and 264 (female:174, male:90) unaffected normal controls (NC) were genotyped for single nucleotide polymorphisms (SNPs) of ACE2 and ANPEP by the high-throughput Sequenom system. 4/12 and 8/12 SNPs of ACE2 and ANPEP respectively were found to have allele frequency >5% in 90 NC samples. These SNPs were further genotyped in the three populations. All the studied SNPs are in Hardy-Weinberg equilibrium in the three populations. As ACE2 is located on sex chromosome, statistical analysis was performed on female and male subgroups. Except for ACE2 SNP rs879922 in female, no significant association was found for the other SNPs tested, both in male and female (p>0.05). The C-allele carriers of SNP rs879922 (dbSNP cluster id) appeared to be associated with lower risk to develop SARS (p=0.004); however, the number of C-allele carriers is too small (6.4% in female, and 2.5% in male in the overall populations) to draw proper conclusions. The G-allele carriers of ANPEP SNP A603G appeared associated with risk (p=0.008). However, allowing for multiple testing, this p value does not yet reach statistical significance. No significant association was found for all the other ANPEP SNPs tested. The presence of other SNPs in the promoters or coding regions of ACE2 and ANPEP are being explored by direct sequencing on the pooled DNA with view to genotyping.