Évaluation de la variabilité génotypique et phénotypique, intrafratrie, dans la dystrophie myotonique de Steinert

La dystrophie myotonique (DM) est caractérisée par Sa grande variabilité de son expression clinique et génétique. Le but de l'étude est d'évaluer dans quelle mesure le degré d'atteinte peut être prédit à î'aide des formes de DM présentes dans une fratrie. La détermination de la force du lien génotype-phénotype, pour 134 patients du Saguenay-Lac-Saint-Jean (SLSJ), indique que le génotype n'est pas suffisant pour prédire la sévérité de î'atteinte, particulièrement lors d'une transmission paternelle. L'évaluation de la variabilité génotypique (n=86 paires de germains) et phénotypique (n=89 paires de germains) révèle peu de variations significatives dans les fratries. Toutefois, compte tenu de Sa présence d'écarts importants, il serait imprudent que le pronostic soit établi uniquement à l'aide de cet outil. Le rang de naissance, l'intervalle intergénésique, le nombre de CTG du plus vieux germain, et î'âge du parent porteur à la naissance de i'enfant peuvent difficilement expliquer ces écarts

Salivary pH as a marker of plasma adiponectin concentrations in Women

<p>Abstract</p> <p>Background</p> <p>Plasma adiponectin is a significant correlate of the pro-inflammatory cardiometabolic risk profile associated with obesity and type 2 diabetes. Salivary pH is influenced by several cardiometabolic risk components such as inflammation, oxidation and numerous oral and systemic health modulators, including the menopausal status. This study aimed to assess the association between plasma adiponectin concentrations and salivary pH in women according to the menopausal status.</p> <p>Method</p> <p>Unstimulated saliva collection was performed in 151 Caucasian women of French-Canadian origin (53 premenopausal women (PMW) and 98 menopausal women (MW)). Student's t test, ANOVA and linear regression models were used to assess the association between plasma adiponectin concentrations and salivary pH.</p> <p>Results</p> <p>Plasma adiponectin levels increased as a function of salivary pH in the whole sample and among MW (r = 0.29 and r = 0.36, p < 0.001). The proportion of the variance of plasma adiponectin levels explained by the salivary pH (R²) was 10.8% (p < 0.001). Plasma adiponectin levels progressively increased across salivary pH quartiles (p = 0.005).</p> <p>Conclusions</p> <p>These results suggest that salivary pH is a significant correlate of plasma adiponectin levels in women. With the increasing prevalence of type 2 diabetes and obesity, new technologies should be developed to more easily monitor health status, disease onset and progression. Salivary pH, a simple, inexpensive and non-invasive measure, could be a very promising avenue.</p

Les bacs appliqués des collèges ontariens : quels enjeux pour le Québec ?

Cette présentation du Conseil supérieur de l’éducation tente de démystifier les bacs appliqués offerts par les collèges ontariens

Genetic burden linked to founder effects in Saguenay–Lac-Saint-Jean illustrates the importance of genetic screening test availability

The Saguenay–Lac-Saint-Jean (SLSJ) region located in the province of Quebec was settled in the 19th century by pioneers issued from successive migration waves starting in France in the 17th century and continuing within Quebec until the beginning of the 20th century. The genetic structure of the SLSJ population is considered to be the product of a triple founder effect and is characterised by a higher prevalence of some rare genetic diseases. Several studies were performed to elucidate the historical, demographic and genetic background of current SLSJ inhabitants to assess the origins of these rare disorders and their distribution in the population. Thanks to the development of new sequencing technologies, the genes and the variants responsible for the most prevalent conditions were identified. Combined with other resources such as the BALSAC population database, identifying the causal genes and the pathogenic variants allowed to assess the impacts of some of these founder mutations on the population health and to design precision medicine public health strategies based on carrier testing. Furthermore, it stimulated the establishment of many public programmes. We report here a review and an update of a subset of inherited disorders and founder mutations in the SLSJ region. Data were collected from published scientific sources. This work expands the knowledge about the current frequencies of these rare disorders, the frequencies of other rare genetic diseases in this population, the relevance of the carrier tests offered to the population, as well as the current available treatments and research about future therapeutic avenues for these inherited disorders

Pharmacogenomics of statin-related myopathy:Meta-analysis of rare variants from whole-exome sequencing

AIMS:Statin-related myopathy (SRM), which includes rhabdomyolysis, is an uncommon but important adverse drug reaction because the number of people prescribed statins world-wide is large. Previous association studies of common genetic variants have had limited success in identifying a genetic basis for this adverse drug reaction. We conducted a multi-site whole-exome sequencing study to investigate whether rare coding variants confer an increased risk of SRM. METHODS AND RESULTS:SRM 3-5 cases (N = 505) and statin treatment-tolerant controls (N = 2047) were recruited from multiple sites in North America and Europe. SRM 3-5 was defined as symptoms consistent with muscle injury and an elevated creatine phosphokinase level >4 times upper limit of normal without another likely cause of muscle injury. Whole-exome sequencing and variant calling was coordinated from two analysis centres, and results of single-variant and gene-based burden tests were meta-analysed. No genome-wide significant associations were identified. Given the large number of cases, we had 80% power to identify a variant with minor allele frequency of 0.01 that increases the risk of SRM 6-fold at genome-wide significance. CONCLUSIONS:In this large whole-exome sequencing study of severe statin-related muscle injury conducted to date, we did not find evidence that rare coding variants are responsible for this adverse drug reaction. Larger sample sizes would be required to identify rare variants with small effects, but it is unclear whether such findings would be clinically actionable

Association between salivary pH and metabolic syndrome in women: a cross-sectional study

Abstract Background The salivary flow rate is an important determinant of salivary pH. It is influenced by several metabolic syndrome (MetS) components as well as the menopausal status. The cluster of cardiometabolic risk factors that characterizes the MetS could be exacerbated following menopause. The objective of this study was therefore to document the association between salivary pH and MetS expression in women according to the menopausal status. Methods In this cross-sectional study, unstimulated saliva collection was performed on 198 Caucasian women of French-Canadian origin of which 55 were premenopausal women (PMW) and 143 menopausal women (MW). Student’s t test, ANOVA and correlation analyses were used to assess the association between salivary pH and MetS components. Results The salivary pH level was significantly correlated with several MetS covariates, namely triglycerides (TG), apolipoprotein B (apo B) and plasma glucose concentrations as well as waist circumference and the number of MetS components present in the whole sample and PMW only. Mean pH levels decreased as the number of MetS components increased (p = 0.004). The correlations between salivary pH and variables associated with MetS components tended to be stronger in PMW. The proportion of the variance (R2) of salivary pH explained by MetS-related variables in PMW, MW and the whole sample was 23.6% (p = 0.041), 18.1% and 17.0% (p  Conclusions The increasing prevalence of obesity calls for the development of new technologies to more easily monitor health status without increasing the burden of healthcare costs. As such, the salivary pH could be an inexpensive screening tool. These exploratory data suggest that salivary pH may be a significant correlate of the expression of MetS components. However, other studies with different populations are needed to confirm these findings before our observations lead to practical use in clinical settings.</p

Non-Alcoholic Fatty Liver in Patients with Chylomicronemia

Non-alcoholic fatty liver disease (NAFLD) is frequent in patients with features of the metabolic syndrome (MetS), obesity, or type 2 diabetes. Lipoprotein lipase (LPL) is the main driver of triglyceride (TG) hydrolysis in chylomicrons and very-low density lipoproteins (VLDL). In some patients with MetS, dysfunction of this pathway can lead to plasma TG values > 10 mmol/L (multifactorial chylomicronemia or MCS). Chylomicronemia also characterizes LPL deficiency (LPLD), a rare autosomal recessive disease called familial chylomicronemia syndrome (FCS), which is associated with an increased risk of recurrent pancreatitis. This study aims to investigate the expression of NAFLD, as assessed by transient elastography, in MCS and FCS subjects. Data were obtained from 38 subjects with chylomicronemia; 19 genetically confirmed FCS and 19 sex- and age-matched MCS. All participants underwent liver ultrasonography and stiffness measurement after a 4-h fast using transient elastography (FibroScan®, Echosens, Waltham, MA, USA). NAFLD (controlled attenuation parameter (CAP) > 280 dB/m) was observed in 42.1% of FCS and 73.7% of MCS subjects (p = 0.05). FCS subjects had lower body mass index (BMI) than MCS. Only 25% of FCS subjects with NAFLD had a BMI ≥ 30 compared to 64.3% in MCS (p = 0.004). In FCS, NAFLD occurred even in the presence of very low (≤18 kg/m2) BMI. In both FCS and MCS, CAP was negatively associated with acute pancreatitis risk. In this study, NAFLD was commonly observed in both FCS and MCS subjects and occurred independently of the BMI and fasting glucose values in FCS; NAFLD was associated with a lower occurrence of acute pancreatitis episodes

Influence of Abdominal Obesity on the Lipid-Lipoprotein Profile in Apoprotein E2/4 Carriers: The Effect of an Apparent Duality

Background. Apolipoprotein (Apo) E plays a key role in the handling of lipoprotein particles with ApoE2 and ApoE4 frequently having opposite effects compared to ApoE3. Some individuals simultaneously carry both E2 and E4 alleles. The impact of the ApoE2/4 genotype on lipid concentrations and its consequences on health remain poorly documented. Objective. This study compared the lipid profile between ApoE2/4 carriers and other ApoE genotypes in relation to the waist circumference. Methods. Cholesterol, triglyceride (TG), and ApoB concentrations were measured among 2,680 Caucasians. Multivariate logistic regression models were used to estimate the contribution of ApoE2/4 to various dyslipidemic profiles associated with abdominal obesity. Results. In presence of abdominal obesity, the lipid profile was as deteriorated in ApoE2/4 carriers as in carriers of other ApoE genotypes. There was a more pronounced effect on TG-rich lipoproteins, particularly in ApoE2/2 (a feature of type III dysbetalipoproteinemia), and non-high-density lipoprotein (HDL) cholesterol in ApoE4/4. Compared to ApoE2/2, ApoE2/4 carriers presented lower very-low-density lipoprotein (VLDL) cholesterol concentrations and VLDL-cholesterol/TG ratios, with or without obesity, and higher low-density lipoprotein (LDL) cholesterol concentrations. Conclusion. In presence of abdominal obesity, the influence of the ApoE2 allele could be less pronounced than that of ApoE4 among ApoE2/4 individuals