p53 polymorphisms in Russia and Belarus: correlation of the 2-1-1 haplotype frequency with longitude

Abstract

Four different polymorphisms in the human p53 gene (a 16-bp duplication in intron 3, and three RFLPs: for Bsh1236I at codon 72, for MspI in intron 6 and for BamHI in the 3' flanking region) and extended haplotypes were studied in nine geographically diverse populations from Russia and Belarus. The Yakuts differed from all other populations, as they had a significantly higher frequency of the BamHI A1 allele. Most populations did not differ significantly from each other in the frequency of the Bsh1236I polymorphism. The 16-bp duplication A1 allele and MspI A2 allele frequencies were significantly higher in the Yakut and Khant populations. Linkage disequilibrium values (D') between BamHI and other polymorphic sites were not significant in many cases; for this reason we have used the 16 bp-Bsh1236I-MspI haplotype frequencies only. Of eight possible haplotypes, five were observed in the populations investigated. Haplotype 1-2-2 was the most frequent in all populations. The next most common haplotype, 1-1-2, was present at very similar frequencies among the Byelorussians and Russians from Smolensk, but was more frequent in other populations. The frequency of haplotype 2-1-1 showed a nearly continuous decrease from West to East (from 17.857% among the Byelorussians to 0.685% in the Yakuts from the Verkhoyansk) and correlated with longitude (Spearman's r = -0.8667, P = 0.0025), which may be due to natural selection and adaptation. The relationships among populations were evaluated by means of Nei's D(A) distances for the 16 bp-Bsh1236I-MspI haplotype frequencies. Based on the multidimensional scaling analysis a correlation between p53 haplotype frequencies and ethnicity is supposed.

Common Genetic Variation in TP53 Is Associated with Lung Cancer Risk and Prognosis in African Americans and Somatic Mutations in Lung Tumors

“…In another study, several haplotypes, or combinations of susceptibility alleles, were associated with lung cancer in Caucasians (37). Despite differences in the alleles examined in these studies and our report, given the observed linkage between the three polymorphisms (35,37,39,44,45) and the position of the haplotype on TP53 associated with lung cancer in our study, our results and previous studies suggest that this region of TP53 may have a role in modulating lung cancer susceptibility. No previous studies examined the association of TP53 haplotypes with lung cancer survival.…”

The P53 pathway: what questions remain to be explored?

“…62 The observation that the ratio of proline to arginine alleles in individuals changes as the latitude changes from the equator to the north pole already suggests that selection is playing a role upon these alleles. 63 There are several studies that suggest that one or the other allele could influence the occurrence or progression of cancer. 64,65 At present however the results are confusing and a better understanding of the role of these two alleles in the pathway will be important.…”

Polymorphisms in the p53 pathway

“…Here, we will present only two polymorphisms that have been shown to impact the function or level of expression of p53, an allele that carries a 16 base-pair (bp) duplication in intron 3 localized at nucleotide 11 951 (denoted þ 16), and an allele that carries a G to C transversion in intron 6 at nucleotide 13 964 (denoted G-C). The allele frequencies of these two non-coding polymorphisms, which show significant differences between populations from Russia and Belarus, have recently been correlated to ethnical variations (Khrunin et al, 2005).…”