A genome-wide linkage scan for 25-OH-D3 and 1,25-(OH)2-D3 serum levels in asthma families

To identify genome regions linked to serum vitamin D metabolites we analyzed 25-OH-D-3 and 1,25-(OH)(2)-D-3 levels from 947 participants of a family study recruited for asthma. From these individuals data were available from a previous genome scan that included 364 autosomal microsatellite marker. 25-OH-D-3 levels showed a heritability of 80% in these families while 1,25-(OH)2-D3 reached only 30%. Genome-wide linkage using variance component analysis showed increased LOD scores for 25-OH-D3 at marker D1S2815 (unadjusted LOD 2.9), D2S2153 (LOD 3.4), D5S2017 (LOD 2.5). D6S260 (LOD 2.1) and D17S1824 (2.5). In contrast, the maximum LOD score for 1,25-(OH)2-D3 level was only 1.2 at marker D17S926. We conclude that only 25-OH-D3 serum levels are under genetic control where several genes are involved. The lead linkage region does not code for enzymes already known in the metabolic pathway of vitamin D and may therefore contain further genes relevant to the regulation of vitamin D serum levels. (c) 2006 Elsevier Ltd. All rights reserved.