摘要
Individuals vary considerably in their susceptibility to infection and ability to recover from apparently similar infectious processes. These differences can be partially explained by polymorphisms of the genes encoding proteins involved in mediating and controlling the innate immune response, the inflammatory cascade, coagulation, and fibrinolysis. There is a much higher heritability of death due to infection than death due to cancer or heart disease. More than 8 million single nucleotide polymorphisms (SNPs) have been detect in the human genome, and there is very little understanding of their effect on gene expression and protein function. The use of haplotypes, which are inherited sets of linked SNPs, as the unit of genetic variation in association studies and the marking of these haplotypes with unique “tag SNPs” may help to narrow down the search for causal SNPs. Future studies must be large (thousands of patients) and must be carefully designed to avoid false associations resulting from ethnic differences in genotype frequencies and disease prevalence in order to find true, reproducible associations between genotype and phenotype. Functional studies and careful characterization of intermediate phenotypes must be done to lend biological plausibility to genotype-phenotype associations.Examination of the association between genetic polymorphisms and sepsis promises to provide clinicians with new tools to evaluate prognosis, to intervene early and aggressively in treating high-risk persons, and to avoid the use of therapies with adverse effects in treating low-risk persons.
Individuals vary considerably in their susceptibility to infection and ability to recover from apparently similar infectious processes. These differences can be partially explained by polymorphisms of the genes encoding proteins involved in mediating and controlling the innate immune response, the inflammatory cascade, coagulation, and fibrinolysis. There is a much higher heritability of death due to infection than death due to cancer or heart disease. More than 8 million single nucleotide polymorphisms （SNPs） have been detect in the human genome, and there is very little understanding of their effect on gene expression and protein function. The use of haplotypes, which are inherited sets of linked SNPs, as the unit of genetic variation in association studies and the marking of these haplotypes with unique ＂tag SNPs＂ may help to narrow down the search for causal SNPs. Future studies must be large （thousands of patients） and must be carefully designed to avoid false associations resulting from ethnic differences in genotype frequencies and disease prevalence in order to find true, reproducible associations between genotype and phenotype. Functional studies and careful characterization of intermediate phenotypes must be done to lend biological plausibility to genotype-phenotype associations. Examination of the association between genetic polymorphisms and sepsis promises to provide clinicians with new tools to evaluate prognosis, to intervene early and aggressively in treating high-risk persons, and to avoid the use of therapies with adverse effects in treating low-risk persons.
出处
《国际麻醉学与复苏杂志》
CAS
2006年第3期189-194,共6页
International Journal of Anesthesiology and Resuscitation
