Deletion Polymorphism of the Human c-fms Gene Intron 11: Allelic Frequencies in Some Populations of Russia and Possible Functional Significance.

Analysis of deletion polymorphism of the human c-fms gene intron 11 (∼425-bp deletion) is of particular interest because of the increased proportion of the heterozygotes among the children born from parents, one of which lacks the deletion-carrying allele, and the other is heterozygous for this allele. In this study, allele and haplotype frequencies of the polymorphism were assessed in a number of Caucasoid and Mongoloid populations of Russia. In all populations tested, relatively high prevalence of the deletion-bearing allele, ranging from 9.45% in ethnic Germans to 20.75% in Altaians, was detected. Russians and Kazakhs were characterized by intermediate frequencies of the rare allele, constituting in these populations 12.89 and 14.93%, respectively. Hardy–Weinberg expectations were met in all populations examined, pointing to a stable level of polymorphism at the c-fms intron 11. It was established by the contextual analysis of the deleted DNA fragment along with the flanking sequences that this region contained a number of transcription factor motifs (ets, CArG, and myc), potentially capable of the regulation of the M-CSF-dependant c-fms transcription. The deletion breakpoint was localized within the CArG motif, which, together with the neighboring ets motif, form the potential CArG/ets composite element. It was suggested that the allele lacking the fragment of intron 11 might be restricted in its ability to modulate the level of the c-fms transcription in response to M-CSF. The molecular epidemiological survey provided indirect evidence favoring the suggestion on the possible functional value of this gene fragment. It was demonstrated that in the samples from acute bronchitis and trichomoniasis patients allelic and genotype frequencies were significantly different from those in the population sample. In case of trichmoniasis, the frequency of rare allele was 2.4 times lower, and in case of acute bronchitis it was 2.1 times higher than in the control sample. [ABSTRACT FROM AUTHOR]