Linkage disequilibrium and haplotype analysis among four novel single-nucleotide polymorphisms in the human leukemia inhibitory factor (LIF) gene

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine implicated in va rious pathological conditions, such as rheumatoid arthritis and osteoporosi s. Despite the possible importance of LIF as a therapeutic target, little i s known about the bioregulation of the human LIF gene. We here sequenced th e entire structure of the LIF gene of 48 alleles in the Japanese population . These experiments identified four single-nucleotide polymorphisms (SNPs) and determined their allelic frequencies from a 48-allele sequence in the J apanese population. All four SNPs found in the LIF gene were located within exon 3, that is, a C/T at nucleotide (nt) position 3951, a C/G at nt posit ion 4376, an A/C at nt position 4442, and a G/A at nt position 5961 (nucleo tide numbering starts from the ATG start codon). Based on the genotypic dat a, we constructed four major haplotypes in the tested population. Two-way c omparisons of SNPs revealed complete linkage disequilibrium between SNPs at positions 3951, 4376, and 4442. These results may prove to be useful as ge netic markers for population-based disease-association studies in osteoporo sis.