Marfan Syndrome Variability: Investigation of the Roles of Sarcolipin and Calcium as Potential Transregulator of FBN1 Expression.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder that displays a great clinical variability. Previous work in our laboratory showed that fibrillin-1 () messenger RNA (mRNA) expression is a surrogate endpoint for MFS severity. Therefore, an expression quantitative trait loci (eQTL) analysis was performed to identify trans-acting regulators of expression, and a significant signal reached genome-wide significant threshold on chromosome 11. This signal delineated a region comprising one expressed gene, (encoding sarcolipin), and a single pseudogene, (CTD-2651C21.3). We first investigated the region and then looked for association between the genes in the region and expression. For the first time, we showed that the gene is weakly expressed in skin fibroblasts. There is no direct correlation between and gene expression. We showed that calcium influx modulates gene expression. Finally, gene expression is highly correlated to that of the neighboring . We were able to confirm the impact of calcium influx on gene expression but we could not conclude regarding the role of sarcolipin and/or the eQTL locus in this regulation.