Identification of three genomic haplotypes 5' to the human CD1D gene and their distribution in four ethnic groups.

CD1d presents lipid antigen to a conserved population of natural killer (NK) T cells, which participate in host immune defense, tumor cell rejection and suppression of autoimmunity. The levels of human CD1d expression vary significantly between individuals. To understand such variation, we sequenced the region up to 1.7 kb 5' upstream of the translation start site and partially through exon 2 in 44 white Americans. We also studied two tagged single nucleotide polymorphisms (SNP) in 112 white Americans, 60 African-Americans, 88 Europeans, and 84 Chinese people from the region. Six SNP present in the region (-836C-->T, -773C-->T, -764C-->G, -713A-->T, -365A-->G and +363A-->G) were found to be in a complete linkage disequilibrium and comprised three haplotypes. Haplotype 1 had -836C, -773C, -764C, -713A, -365A and +363A. Haplotype 2 had -836C, -773T, -764C, -713A, -365A and +363A. Haplotype 3 had -836T, -773C, -764G, -713T, -365G and +363G. -773C-->T and -764C-->G can serve as the tagged SNP to differentiate the three haplotypes. The frequency of haplotype 1 was significantly higher in African Americans than in the other three ethnic groups, whereas the frequency of haplotype 3 was significantly higher in the Chinese people than those in the other three groups. The finding of the three haplotypes provides a genetic marker for CD1d and facilitates the study of the functional role of the genetic variations in human CD1d expression and regulation.