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

IL-12R has previously been reported to be associated with infectious diseases such as tuberculosis, hepatitis B virus infection, and parvovirus infection [22] [23] [24] , revealing its potential role of function in host defense against microbial infections. We genotyped 4 SNPs (+705A/G, +1158T/C , +1196G/C and +1664 C/T) that have been alleged to cause missense mutations of the IL-12 RB1 gene in SARS patients , close contacts and healthy controls. These four SNPs (one novel) have been confirmed to cause missense variants in the extracellular coding sequence of the IL12RB1gene. These four SNPs lie within 6.2-kb span of genomic DNA on chromosome 19p13.1. It is suggested that one or more of the four missense variants could affect the quality (or quantity) of the gene products and cause mild functional impairment in the receptor's responsiveness to IL-12 [25] . The results show that individuals with 1664 C/T (CT) and (TT) genotype were at increased risk of susceptibility to SARS infection. When only severe patients were considered, the significance disappeared, in comparison with the mild patients. We also estimated the frequencies of IL-12 RB1 haplotypes, which composed of 4 polymorphic alleles, and identified risk haplotype (GCCT) that might confer genetic susceptibility to SARS infection. In agreement with this finding, the +1664 C/T (T) allele was among the risk haplotypes GCCT, whereas the alternative C allele was among the protective haplotype (GCCC). These findings support the association between IL12B1 polymorphism and SARS infection, but not necessary the disease outcome in Chinese population.