To: Biason-Lauber A, Boehm B, Lang-Muritano M et al. (2005) Association of childhood type 1 diabetes mellitus with a variant of PAX4: possible link to beta cell regenerative capacity. Diabetologia 48:900–905

Comment on: Biason-Lauber A, Boehm B, Lang-Muritano M, et al (2005) Association of childhood type 1 diabetes mellitus with a variant of PAX4: possible link to beta cell regenerative capacity. Diabetologia 48:900–905

“…The discrepancy between our data and the report by Biaison-Lauber et al may be explained by genetic heterogeneity for the association between PAX4 and type 1 diabetes. However, the associations reported there were possibly spurious and may not reflect a causal relation between PAX4 and type 1 diabetes, since two other studies [6,7], in addition to this report, were unable to confirm the association. Furthermore, the departure from HardyWeinberg equilibrium in both control populations studied in the initial report may indicate major genotyping errors [8].…”

Genetic epidemiology of type 1 diabetes

“…However, several readers identified that there was significant deviation of the genotypes from the Hardy-Weinberg equilibrium in both the cases and controls from Switzerland and Germany [57][58][59][60]. Deviation from the Hardy-Weinberg equilibrium may result from violations of any of the assumptions (including recent admixture, selection, migration) and is also commonly used as a quality control measure for genotyping assays.…”

“…However, it would be unexpected to observe significant deviation in both cases and controls, unless the allele is under selection [61]. Attempts to replicate the association in both a large collection of families as well as in a large case-control study failed (P > 0.1), as did casecontrol studies from Finland and Hungary (P > 0.5) [58], and family-based studies in Denmark [57]. Of particular importance, none of the groups that attempted to replicate the association observed significant deviation from the Hardy-Weinberg equilibrium in either cases or controls, suggesting that there may be technical problems with the genotyping assay in the initial report.…”

Produção e uso da proteína de fusão VP22.Pax4 na diferenciação de células-tronco em células produtoras de insulina

“…Estudos associando mutações no gene PAX4 ao Diabetes ainda são um pouco controversos. Alguns grupos não encontraram correlação alguma com o Diabetes tipo 1 (HOWSON et al, 2009;GYLVIN et al, 2005;MAIER et al, 2005), contradizendo os estudos feitos em escandinavos (HOLM et al, 2004), e em crianças suíças e alemãs (BIASON-LAUBER et al, 2005) portadores de DM1, onde os autores afirmam que mutações no PAX4 podem estar diretamente ligadas ao desenvolvimento da doença.…”