Human brain weight is correlated with expression of the ‘housekeeping genes’ beta-2-microglobulin (β2M) and TATA-binding protein (TBP)

Abstract

Many variables affect mRNA measurements in post mortem human brain tissue. Brain weight has not hitherto been considered to be such a factor. This study examined whether there is any relationship between brain weight and mRNA abundance. We investigated quantitative real-time RT-PCR data for five 'housekeeping genes' using the 104 adult brains of the Stanley Microarray Consortium series. Eleven data sets were analysed, from cerebellum, hippocampus, and anterior cingulate cortex. We used a specified sequence of correlations, partial correlations and multiple regression analyses. Brain weight correlated with the 'raw' (i.e. non-normalized) data for two mRNAs, β2-microglobulin and TATA-binding protein, measured in cerebellum and hippocampus, respectively. In hippocampus, the geometric mean of three housekeeping gene transcripts also correlated with brain weight. The correlations were significant after adjusting for age, sex and other confounders, and the effect of brain weight was confirmed using multiple regression. No correlations with brain weight were seen in the anterior cingulate cortex, nor for the other mRNAs examined. The findings were not anticipated; they need replication in another brain series, and a more systematic survey is indicated. In the interim, we suggest that quantitative gene expression studies in human brain should inspect for a potential influence of brain weight, especially as the affected transcripts are commonly used as reference genes for normalization purposes in studies of neurological and psychiatric disorders. The relationship of brain weight with β2-microglobulin mRNA may reflect the roles of major histocompatibility complex class I genes in synapse formation and plasticity.