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 is interesting to note that these associations only exist when close contacts were used as a control group. When healthy blood donors were used as controls, no association could be detected. We reasoned that genetic difference between the two control groups might partly account for the distinct observations with regard to SARS susceptibility, i.e. close contacts might be more immunogenetically resistant to SARS infection than healthy controls. In this case, close contacts might serve as more suitable controls healthy individuals, who had never been exposed to SARS-CoV. It's as well intriguing that the pattern of polymorphism in +1664 C/T in SARS patients deviated slightly from Hardy-Weinberg equilibrium. As noted in the previous study [26] , detection of HW disequilibrium at SNP loci in the case sample could be an indicator that a disease/susceptibility gene is within the region. There are also other possibilities indicated, like that a pseudo-SNP is present, DNA contamination, or a genotyping error, however, these latter possibilities are unlikely since we have duplicated the genotyping assay for all the samples with ambiguous results through sequencing. This also can be argued from the observed perfect adherence to Hardy-Weinberg disequilibrium from control group. The chance of subgroup is minor, since all the subjects were Chinese Han population without consanguineous relationship. Taken together, we suggested this deviation was from the correlation between genetic variant and disease, instead of false association.