Hyperlipidemias: Adlouni A

El Messal M, Aït Chihab K, Chater R, Loutfi M, Kettani A, Hafidi A, Adlouni A. · Groupe de Génétique et Biologie Moléculaire, Laboratoire de Biochimie, Faculté des Sciences Aïn Chock, Casablanca , Morocco. · Acta Cardiol. · Pubmed #17117756 No free full text.

Abstract: Familial hypercholesterolaemia (FH) is an autosomal dominant disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C) as a result of mutations that impair their removal from plasma.The clinical consequence is a high risk of premature cardiovascular disease. Because of the extreme risk of mortality and morbidity, diagnosis, recruitment and management of FH patients must be one of the priorities of public health. In Morocco, specialized consultation for dyslipidaemia and strategy for management of this cardiovascular major risk factor does not exist, making FH identification and management difficult. In this review, we present the first FH state of the art in our country through a sample of 66 subjects. By this analysis, we have tried to elucidate some points that impede the identification and recruitment of heterozygous FH and the management of both heterozygous and homozygous FH in Morocco. Also, we have attempted to propose some strategies for an adequate management of FH in our country, taking into account the local specifications.

Ait Chihab K, Chater R, Cenarro A, Kettani A, Castillo S, Loutfi M, Ribalta J, Adlouni A, Pocovi M, El Messal M. · Laboratoire de Biochimie et Biologiè Moleculaire, Groupe de Génétique et Biologie Molèculaire, Faculté des Sciences, Ain chock. B. P. 5366, Casablanca, Morocco. · J Genet. · Pubmed #17968143 links to  free full text

This publication has no abstract.

Chater R, Aït Chihab K, Rabès JP, Varret M, Chabraoui L, El Jahiri Y, Adlouni A, Boileau C, Kettani A, El Messal M. · Laboratoire de Biochimie, Groupe de Génétique et Biologie Moléculaire, Faculté des Sciences Aïn Chock, BP: 5366 Maarif, Casablanca, Morocco. · Clin Chim Acta. · Pubmed #16806138 No free full text.

Abstract: BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Until now, molecular data concerning FH in Morocco is still limited. To gain more information in this field and to assess the contribution of these three genes in the cause of FH determinism, we analyzed six unrelated Moroccan probands and twenty-five of their family's members. METHODS: After LDLR and APOB genotype analysis, we screened the LDLR gene for mutations using southern blot and PCR-sequencing analysis. We also screened the APOB gene for the two common mutations R3500Q and R3531C by PCR-mediated site-directed mutagenesis. The PCSK9 gene was analyzed by direct sequencing. RESULTS: We identified three novel mutations (C25X, IVS3+5G>T, D558A) and two mutations previously described (D151N, A480E) in the LDLR gene. The R3500Q and R3531C mutations are absent in our probands and for 1 proband, the implication of LDLR, APOB and PCSK9 genes was excluded, supporting the implication of a fourth gene in the determination of FH. CONCLUSION: These data are in agreement with our previous study that suggests a heterogeneous mutational spectrum of FH in Morocco.

El Messal M, Beaudeux JL, Drissi A, Giral P, Chater R, Bruckert E, Adlouni A, Chapman MJ. · Faculté des Sciences Aïn Chock, Université Hassan II Aïn Chock, Casablanca, Morocco. · Clin Chim Acta. · Pubmed #16280123 No free full text.

Abstract: BACKGROUND: Familial hypercholesterolemia (FH) is a common inherited disorder of lipoprotein metabolism, whose origin involves mutations in the gene coding for the low-density lipoprotein receptor protein. Although FH is monogenic, wide variation occurs in the onset and severity of atherosclerosis in these patients. METHODS: Since data on levels of inflammatory proteins and/or active factors in FH patients who have never received lipid-lowering treatment are lacking, serum levels of MMP-3, active MMP-9 and TIMP-1 as well as pro-inflammatory cytokines (TNF-alpha, IL-18) were determined in never-treated homozygous FH Moroccan patients (n=4) and compared to those of heterozygous FH subjects (n=7) and of healthy control subjects (n=5). RESULTS: When compared to controls, homozygous FH patients exhibited levels of active MMP-9 and TIMP-1 (p<0.05), and of both high sensitive-CRP and IL-18 which were significantly elevated (p<0.05 and p<0.01, respectively). In heterozygous FH patients, intermediate values between FH homozygotes and healthy controls were observed for these markers, with the exception of MMP-9 activity whose levels were significantly elevated (p<0.05). Multivariate analysis revealed a positive correlation between apolipoprotein B, TIMP-1 and IL-18 levels, and between hs-CRP and IL-18 (p<0.01). CONCLUSIONS: Although the sample size of this FH group was limited, our data suggest that nontreated homozygous FH patients, and to a lesser degree heterozygous FH patients, exhibit not only a markedly proinflammatory vascular state but also pronounced extracellular matrix remodeling, as reflected by elevated circulating levels of inflammatory cytokines and MMPs.

El Messal M, Aït Chihab K, Chater R, Vallvé JC, Bennis F, Hafidi A, Ribalta J, Varret M, Loutfi M, Rabès JP, Kettani A, Boileau C, Masana L, Adlouni A. · Laboratoire de Biochimie, Faculté des Sciences Aïn Chock, Km 8, Route d'El Jadida, BP 5366, Maarif, Casablanca, Morocco. · J Hum Genet. · Pubmed #12730724 No free full text.

Abstract: Familial hypercholesterolemia (FH) is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor (LDLR) gene, although it can also be due to alterations in the gene encoding apolipoprotein B (familial defective apoB or FDB) or in other unidentified genes. In Morocco, the molecular basis of FH is unknown. To obtain information on this issue, 27 patients with FH from eight unrelated families were analyzed by screening the LDLR (PCR-SSCP and Southern blot) and apoB genes (PCR and restriction enzyme digestion analysis). None of the patients carried either the R3500Q or the R3531C mutation in the apoB gene. By contrast, seven mutations in the LDLR gene were identified, including five missense mutations on exons 4, 6, 8, and 14 (C113R, G266C, A370T, P664L, C690S) and two large deletions (FH Morocco-1 and FH Morocco-2). The two major rearrangements and the missense mutation G266C are novel mutations and could well be causative of FH in the Moroccan population. This study has yielded preliminary information on the mutation spectrum of the LDLR gene among patients with FH in Morocco.

Adlouni A, El Messal M, Saïle R, Parra H, Fruchart J, Ghalim N. · Laboratoire de Recherche sur les Lipoprotéines, Faculté des Sciences Ben Msik, Sidi Othman, 7955, Casablanca, Morocco. · Atherosclerosis. · Pubmed #10998472 No free full text.

Abstract: In order to investigate the effect of Probucol therapy on reverse cholesterol transport, apo AI-containing lipoprotein particles were isolated and characterized, and their cholesterol effluxing capacity and LCAT activity were assayed in four familial hypercholesterolemia patients before and after 12 weeks of Probucol therapy. Four major subpopulations of apo A-containing lipoprotein particles are separated before and after drug treatment; LpAI, LpAI:AII, LpAIV, LpAI:AIV:AII. Probucol reduces both total plasma and LDL-cholesterol (-17 and -14%, respectively). Apo B decreases slightly (-7.6%). Plasma HDL-cholesterol and apo AI decrease by 36.6 and 34.7%. LpA-I showed a marked decrease (-46%). Moreover, plasma LCAT and CETP activities were markedly increased under Probucol treatment. Analysis of lipoprotein particles showed that Probucol induces a decrease of protein content and an increase of cholesterol and triglycerides contents. Interestingly, Probucol induces an enhancement of LCAT activity in LpAI (4.5-fold). This drug induces a trend toward greater cholesterol efflux from cholesterol-preloaded adipose cells promoted by Lp AI and Lp AIV but not by Lp AI:AII. This study confirms the hypothesis, in addition to the lowering LDL-cholesterol levels and antioxidant effects of Probucol, that HDL reduction was not an atherogenic change in HDL system but may cause an antiatherogenic action by accelerating cholesterol transport through HDL system, promoting reverse cholesterol transport from peripheral tissues.