ABSTRACT
Predisposition towards a TH1 or TH2 type cytokine response is thought to be influenced, at least in part, by inherited combinations of single nucleotide polymorphisms (SNPs) and polymorphic haplotypes within key cytokine genes. One explanation of how genotype affects phenotype in this way is that SNPs within the promoter or other regulatory sequences of certain cytokine genes influence up-regulation or down-regulation of transcription, and thus protein levels. Genetic polymorphism has been identified within virtually all cytokine, cytokine receptor, and receptor antagonist genes. Some of the polymorphisms have been uncovered by alignment of overlapping contiguous sequences and other sequenced clones as part of the human genome project (see https://genome.cse.ucsc.edu/ and https://www. ensembl.org/index.html). More recently, attempts have been made by individual groups and by organized collaborations to validate the occurrence and frequency of these SNPs, and to search for others within a variety of ethnic groups (see https://snpper.chip.org/bio/ snpper-enter/). It is becoming clear that the combinatorial arrangements of SNPs within a gene (haplotypes) and within adjacent genes (extended haplotypes) may provide more
appropriate predictors of genotype-phenotype correlations in population genetics, gene expression, and disease association. As a corollary, there are now several ongoing large-scale projects generating genome-wide haplotype and extended haplotype data (see https:// www.hapmap.org/, https://pga.gs.washington.edu/finished_genes.html and https://www.niehs. nih.gov/envgenom/snpsdb.htm).
