Association of HLA class I with severe acute respiratory syndrome coronavirus infection.
BACKGROUND
The human leukocyte antigen (HLA) system is widely used as a strategy in the search for the etiology of infectious diseases and autoimmune disorders. During the Taiwan epidemic of severe acute respiratory syndrome (SARS), many health care workers were infected. In an effort to establish a screening program for high risk personal, the distribution of HLA class I and II alleles in case and control groups was examined for the presence of an association to a genetic susceptibly or resistance to SARS coronavirus infection.


METHODS
HLA-class I and II allele typing by PCR-SSOP was performed on 37 cases of probable SARS, 28 fever patients excluded later as probable SARS, and 101 non-infected health care workers who were exposed or possibly exposed to SARS coronavirus. An additional control set of 190 normal healthy unrelated Taiwanese was also used in the analysis.


RESULTS
Woolf and Haldane Odds ratio (OR) and corrected P-value (Pc) obtained from two tails Fisher exact test were used to show susceptibility of HLA class I or class II alleles with coronavirus infection. At first, when analyzing infected SARS patients and high risk health care workers groups, HLA-B*4601 (OR = 2.08, P = 0.04, Pc = n.s.) and HLA-B*5401 (OR = 5.44, P = 0.02, Pc = n.s.) appeared as the most probable elements that may be favoring SARS coronavirus infection. After selecting only a "severe cases" patient group from the infected "probable SARS" patient group and comparing them with the high risk health care workers group, the severity of SARS was shown to be significantly associated with HLA-B*4601 (P = 0.0008 or Pc = 0.0279).


CONCLUSIONS
Densely populated regions with genetically related southern Asian populations appear to be more affected by the spreading of SARS infection. Up until recently, no probable SARS patients were reported among Taiwan indigenous peoples who are genetically distinct from the Taiwanese general population, have no HLA-B* 4601 and have high frequency of HLA-B* 1301. While increase of HLA-B* 4601 allele frequency was observed in the "Probable SARS infected" patient group, a further significant increase of the allele was seen in the "Severe cases" patient group. These results appeared to indicate association of HLA-B* 4601 with the severity of SARS infection in Asian populations. Independent studies are needed to test these results.
Lin
Marie
M
Transfusion Medicine Laboratory, Mackay Memorial Hospital, Taipei, Taiwan. marilin@ms2.mmh.org.tw
Tseng
Hsiang-Kuang
HK
Trejaut
Jean A
JA
Lee
Hui-Lin
HL
Loo
Jun-Hun
JH
Chu
Chen-Chung
CC
Chen
Pei-Jan
PJ
Su
Ying-Wen
YW
Lim
Ken Hong
KH
Tsai
Zen-Uong
ZU
Lin
Ruey-Yi
RY
Lin
Ruey-Shiung
RS
Huang
Chun-Hsiung
CH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction / Q000379:methods; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology; D045169:Severe Acute Respiratory Syndrome / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D013624:Taiwan
D015234:HLA-A Antigens; D015235:HLA-B Antigens; C469674:HLA-B*46:01 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I