A bias in genotyping the miR-27a rs895819 and rs11671784 variants.

摘要: Due to the oncogenetic function of miR-27a, SNPs affecting this gene are frequently investigated for an influence on cancer risk. Yang et al. [1] has reported association between minor [G] allele rs895819 miR-27a and a reduced familial breast risk in German population by direct sequencing. One study Chinese Han also observed tumor suppressive effect gastric using MALDITOF MassARRAY [2]. very recent publication analysed with Italian TaqMan allelic discrimination assay [3]. However, genotyping method appears be inappropriate (chr19:13808292) due adjacent variant rs11671784 (chr19:13808296, which is located only 4 nucleotides distance represents rare variant, [T] frequency 2.4 % 1.9 cases healthy controls, respectively [1]). Unfortunately, commercially available pre-designed assays Applied Biosystems do not consider (especially low frequency) their probe design nor provide access sequences [4]. Any overlapping respective other SNP will give false calls case certain constellations. To sure about primer design, we ordered self-designed probes Assay-by-Design service. The two comprise target sites avoid any overlap (please see primers Table 1). bias introduced was as follows: First, genotyped 1,217 patients 1,422 unrelated controls samples described both sequencing method. All uncertain or inconsistent genotypes determined were second time confirmation. As result, concordant our results (Table 2). genotype constellation rs895819-AA/rs11671784-TT all failed when genotyping; rs895819-AG/ rs11671784-CT resulted rs895819-GG instead rs895819-AG Remarkably, researchers notify via duplicates same duplicates. frequencies rs895819-AG/rs11671784-CT rather Caucasian (about 1.4 [1]), it possible that Hardy–Weinberg equilibrium (HWE) although biased assay. Nevertheless, might have important implications final result. We further subset 413 containing R. (&) B. Burwinkel Helmholtz-University Group Molecular Epidemiology, Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany e-mail: r.yang@dkfz.de