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

Genes

Nadine Hanna¹  Pauline Arnaud²  Guillaume Jondeau²  Catherine Boileau²  Mélodie Aubart²  Louise Benarroch²  Marie-Sylvie Gross²  Marie-Paule Jacob² 

[1] Département de Génétique, Centre Hospitalo-Universitaire Xavier Bichat, 46 rue Henri 17 Huchard, 75018 Paris, France;Laboratory for Vascular Translational Science, INSERM U1148, Centre Hospitalo-Universitaire Xavier Bichat, 46 rue Henri Huchard, 75018 Paris, France;

关键词: Marfan syndrome;    variability;    fibrillin-1;    calcium;    sarcolipin;    genetic modifiers;   

DOI  :  10.3390/genes9090421

来源: DOAJ

【 摘 要 】

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 (FBN1) 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 FBN1 expression, and a significant signal reached genome-wide significant threshold on chromosome 11. This signal delineated a region comprising one expressed gene, SLN (encoding sarcolipin), and a single pseudogene, SNX7-ps1 (CTD-2651C21.3). We first investigated the region and then looked for association between the genes in the region and FBN1 expression. For the first time, we showed that the SLN gene is weakly expressed in skin fibroblasts. There is no direct correlation between SLN and FBN1 gene expression. We showed that calcium influx modulates FBN1 gene expression. Finally, SLN gene expression is highly correlated to that of the neighboring SNX7-ps1. We were able to confirm the impact of calcium influx on FBN1 gene expression but we could not conclude regarding the role of sarcolipin and/or the eQTL locus in this regulation.

【 授权许可】

Unknown