Çaku Artuela, Seidah Nabil G, Lortie Audrey, Gagné Nancy, Perron Patrice, Dubé Jean, Corbin Francois
Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Nabil G. Seidah, Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute, affiliated to the Université de Montréal, Montréal, Québec, Canada.
PLoS One. 2017 Mar 23;12(3):e0174301. doi: 10.1371/journal.pone.0174301. eCollection 2017.
Fragile X Syndrome (FXS) is the main genetic cause of autism and intellectual deficiency resulting the absence of the Fragile X Mental Retardation Protein (FMRP). Clinical picture is characterized by cognitive impairment associated with a broad spectrum of psychiatric comorbidities including autism spectrum disorders and attention-deficit/hyperactivity disorders. Some of these disorders have been associated with lipid abnormalities and lower cholesterol levels. Since lipids are important for neuronal development, we aim to investigate the lipid profile of French Canadian-FXS individuals and to identify the altered components of cholesterol metabolism as well as their association with clinical profile.
Anthropometric data were collected from 25 FXS individuals and 26 controls. Lipid assessment included: total cholesterol (TC), triglycerides, LDL, HDL, ApoB, ApoA1, PCSK9, Lp(a) and lipoprotein electrophoresis. Aberrant and adaptive behaviour of affected individuals was respectively assessed by the ABC-C and ABAS questionnaires.
FXS participants had a higher body mass index as compared to controls while 38% of them had TC<10th percentile. Lower levels of LDL, HDL and apoA1 were observed in FXS group as compared to controls. However, PCSK9 levels did not differ between the two groups. As expected, PCSK9 levels correlated with total cholesterol (rs = 0.61, p = 0.001) and LDL (rs = 0.46, p = 0.014) in the control group, while no association was present in the FXS group. An inverse relationship was observed between total cholesterol and aberrant behaviour as determined by ABC-C total score.
Our results showed the presence of hypocholesterolemia in French Canadian-FXS population, a condition that seems to influence their clinical phenotype. We identified for the first time a potential underlying alteration of PCSK9 function in FXS that could result from the absence of FMRP. Further investigations are warranted to better understand the association between cholesterol metabolism, PCSK9, FMRP and clinical profile.
脆性X综合征（FXS）是自闭症和智力缺陷的主要遗传病因，由脆性X智力低下蛋白（FMRP）缺失所致。临床症状以认知障碍为特征，并伴有广泛的精神疾病共病，包括自闭症谱系障碍和注意力缺陷多动障碍。其中一些疾病与脂质异常和较低的胆固醇水平有关。由于脂质对神经元发育很重要，我们旨在研究法裔加拿大FXS患者的血脂谱，确定胆固醇代谢的改变成分及其与临床特征的关联。
收集了25名FXS患者和26名对照者的人体测量数据。脂质评估包括：总胆固醇（TC）、甘油三酯、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、载脂蛋白B（ApoB）、载脂蛋白A1（ApoA1）、前蛋白转化酶枯草溶菌素9（PCSK9）、脂蛋白（a）[Lp（a）]和脂蛋白电泳。分别通过ABC-C问卷和ABAS问卷评估受影响个体的异常行为和适应性行为。
与对照组相比，FXS参与者的体重指数更高，其中38%的人TC<第10百分位数。与对照组相比，FXS组的LDL、HDL和apoA1水平较低。然而，两组之间的PCSK9水平没有差异。正如预期的那样，对照组中PCSK9水平与总胆固醇（rs = 0.61，p = 0.001）和LDL（rs = 0.46，p = 0.014）相关，而FXS组中不存在这种关联。通过ABC-C总分确定，总胆固醇与异常行为之间存在负相关。
我们的结果表明，法裔加拿大FXS人群存在低胆固醇血症，这种情况似乎会影响他们的临床表型。我们首次确定了FXS中PCSK9功能可能存在潜在的潜在改变，这可能是由于FMRP缺失所致。有必要进行进一步研究，以更好地理解胆固醇代谢、PCSK9、FMRP和临床特征之间的关联。
