Open AccessInterleukin 1‐β responses to bacterial toxins and sudden infant death syndrome
Author(s) -
Moscovis Sophia M.,
Gordon Ann E.,
Hall Sharron T.,
Gleeson Maree,
Scott Rodney J.,
RobertsThomsom June,
Weir Donald M.,
Busuttil Anthony,
Blackwell C.Caroline
Publication year - 2004
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1016/j.femsim.2004.06.005
Subject(s) - sudden infant death syndrome , single nucleotide polymorphism , incidence (geometry) , genotype , snp , allele frequency , sudden death , biology , ethnic origin , medicine , pediatrics , genetics , gene , population , physics , environmental health , optics
We tested the hypothesis that significantly higher IL‐1β responses to toxic shock syndrome toxin (TSST) noted for parents of sudden infant death syndrome (SIDS) infants might be due in part to genetic factors such as the IL‐1β (C‐511T) and IL‐1RN (T+2018C) single nucleotide polymorphisms (SNP). The first objective was to assess the distribution of these polymorphisms among SIDS infants, parents of SIDS infants and controls, and two ethnic groups: Aboriginal Australians who have a high incidence of SIDS; and Bangladeshis who in Britain have a low incidence of SIDS compared with Europeans. The second objective was to assess IL‐1β responses to endotoxin and toxic shock syndrome toxin (TSST) from leukocytes of smokers and non‐smokers in relation to these polymorphisms. There were major differences in the distributions of the IL‐1β (C‐511T) SNP between Europeans and Bangladeshis ( p =0.00 ) and between Europeans and Aboriginal Australians ( p =0.00 ); however, they were similar for the Bangladeshi and Aboriginal Australian subjects. The allele frequency distribution of the IL‐1RN (T+2018C) SNP for the Aboriginal Australians was statistically different from the European group ( p =0.00 ), but it was not different from the Bangladeshi group ( p =0.09 ). Compared with controls of European origin, there were no significant differences in the distribution of these polymorphisms among SIDS infants or parents of SIDS infants. For the IL‐1β (C‐511T) SNP, the highest IL‐1β responses to endotoxin were obtained with leukocytes of non‐smokers with the heterozygous CT genotype. Smokers had significantly lower levels of IL‐1β in response to endotoxin ( p =0.01 ) and these differences were significant for donors with the wild type CC ( p =0.00 ) and CT ( p =0.03 ) genotypes. Similar patterns were observed for IL‐1β responses to TSST, but the differences were not significant. For the IL‐1RN (T+2018C) SNP, the highest IL‐1β responses to endotoxin were obtained with leukocytes from non‐smoker donors with the wildtype TT genotype and significantly lower responses were found with leukocytes from donors with the TC genotype ( p =0.02 ). The responses of smokers were lower but the differences were significant only for donors with the TT genotype ( p =0.00 ). Similar patterns were observed for IL‐1β responses to TSST, but the differences were not significant. IL‐1β responses to both endotoxin and TSST were increased for the small number of smokers with the TT genotype of the IL‐1β (C‐511T) SNP. The TT genotype of the IL‐1β (C‐511T) was found predominantly among Aboriginal Australian and Bangladeshi individuals but only a small proportion of Europeans. Smokers with the AA genotype of the IL‐10 (G‐1082A) SNP which is found predominantly among these two groups had significantly lower levels of IL‐10 responses. If cigarette smoke enhances pro‐inflammatory responses and reduces anti‐inflammatory responses in individuals with these genotypes, this might partly explain the increased susceptibility of Aboriginal Australian infants to infections and SIDS.