Regional HLA Differences in Poland and Their Effect on Stem Cell Donor Registry Planning

<div><p>Regional HLA frequency differences are of potential relevance for the optimization of stem cell donor recruitment. We analyzed a very large sample (<i>n</i> = 123,749) of registered Polish stem cell donors. Donor figures by 1-digit postal code regions ranged from <i>n</i> = 5,243 (region 9) to <i>n</i> = 19,661 (region 8). Simulations based on region-specific haplotype frequencies showed that donor recruitment in regions 0, 2, 3 and 4 (mainly located in the south-eastern part of Poland) resulted in an above-average increase of matching probabilities for Polish patients. Regions 1, 7, 8, 9 (mainly located in the northern part of Poland) showed an opposite behavior. However, HLA frequency differences between regions were generally small. A strong indication for regionally focused donor recruitment efforts can, therefore, not be derived from our analyses. Results of haplotype frequency estimations showed sample size effects even for sizes between <i>n</i>≈5,000 and <i>n</i>≈20,000. This observation deserves further attention as most published haplotype frequency estimations are based on much smaller samples.</p></div

HF of the 20 most frequent haplotypes of the total donor file (<i>n</i> = 123,749) in 100 random samples (<i>n</i> = 5,000) of this file (displayed are mean values and 95% confidence intervals for each haplotype; mean values and corresponding haplotypes are given in Supporting Information S1), in 10 regional sub-files (<i>n</i> = 5,000) and in a German sample (<i>n</i> = 5,000).

<p>HF of the 20 most frequent haplotypes of the total donor file (<i>n</i> = 123,749) in 100 random samples (<i>n</i> = 5,000) of this file (displayed are mean values and 95% confidence intervals for each haplotype; mean values and corresponding haplotypes are given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073835#pone.0073835.s001" target="_blank">Supporting Information S1</a>), in 10 regional sub-files (<i>n</i> = 5,000) and in a German sample (<i>n</i> = 5,000).</p

Regional distribution of study donors (<i>n</i> = 123,749) and population figures of Polish 1-digit postal code regions as of June 30, 2010.

<p>© GfK-Geomarketing, Bruchsal, Germany.</p

Simulated matching probabilities by donor file size for various populations of newly recruited donors.

<p>Light green, Polish 1-digit postal code region 0; dark green, 1; yellow, 2; orange, 3; red, 4; violet, 5; turquoise, 6; light blue, 7; dark blue, 8; black, 9; grey, Germany. Donor file sizes range to <i>n</i> = 2,500,000 (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073835#pone-0073835-g004" target="_blank">Figure 4a</a>) and <i>n</i> = 1,700,000 (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073835#pone-0073835-g004" target="_blank">Figure 4b</a>), respectively.</p

1-digit postal code regions in Poland (© www.bacher.de; © GfK-Geomarketing, Bruchsal, Germany).

<p>1-digit postal code regions in Poland (© <a href="http://www.bacher.de" target="_blank">www.bacher.de</a>; © GfK-Geomarketing, Bruchsal, Germany).</p

Overview on various parameters related to the suitability of Polish 1-digit postal code regions for further stem cell donor recruitment efforts.

<p>HT = haplotype, <i>n</i> = total donor file size (including donors already registered at the starting point of the simulation), <i>f</i> = cumulated haplotype frequency, <i>d</i> = genetic distance, R = rank. Small ranks suggest high suitability for donor recruitment. Examples: Region 2 has rank 1 concerning Polish-German genetic distances as it has the <i>highest</i> distance to the German population. Region 6 has rank 1 concerning Polish-Polish genetic distances as it has the <i>lowest</i> mean distance to the other Polish regions.</p