IL-12 RB1 Genetic Variants Contribute to Human Susceptibility to Severe Acute Respiratory Syndrome Infection among Chinese

Tang, Fang; Liu, Wei; Zhang, Fang; Xin, Zhong-Tao; Wei, Mao-Ti; Zhang, Pan-He; Yang, Hong; Ly, Hinh; Cao, Wu-Chun

It should be mentioned not all of the subjects were genotyped due to the inadequacy of DNA samples. Especially for the +C1664T SNP, different percentages of genotypes were missing from SARS, Control A, and Control B groups (18.2%, 6.4% and 3.2% respectively). One can reasonably argue there was another SNP that accounted for the increased fraction of subjects without the defined genotypes in the SARS patient group. It can also be argued that the significant SNPs actually are not functional variants of the IL-12RB1 protein, but instead it is presumably in linkage disequilibrium with a potential functional variant(s) in other loci of the gene. Presently 15 coding, nonsynonymous SNPS are listed in the Entrez database dbSNP, out of a total of 274 known human SNPs for IL12RB1, however, the genotyping for other SNPs in small group of the current population showed MAF (minor allele frequency) of less than 5% (unpublished data). We thus propose the lack of a complete analysis of the SNPS in this gene can pose no severe damage to the study. Still we could not formally exclude possible additional causal variation(s) elsewhere in the gene. The sequencing of the exon and the promoter regions of the IL12RB1 gene from the SARS patient cohort could be helpful in identifying other SNPs which could alter the gene expression level. It would also be warranted to examine whether the same association is observed in other ethnic groups. On the other hand, a relatively small sample size inevitably resulted in limitations of the power to detect significant association in disease outcome. As such, the negative results on SNPs for disease outcome revealed in this study do not necessarily exclude their association with SARS.