Homozygous familial hypercholesterolemia among French Canadians in Québec Province.

Moorjani, Sital; Roy, Madeleine; Gagné, Claude; Davignon, Jean; Brun, Daniel; Toussaint, Mathilda J. M.; Lambert, Marie; Campeau, Lucien; Blaichman, Shirley; Lupien, Paul J.

doi:10.1161/01.atv.9.2.211

Cited by 162 publications

(84 citation statements)

References 26 publications

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“…The 2 test was used to analyze associations in contingency tables. Differences in age, weight, height, BMI, mean baseline levels and percentage changes of plasma lipids, lipoproteins and apoprotein concentrations among the different genetic groups were assessed by one-way ANOVA using Fisher post hoc test when a significant group effect was observed.…”

Section: Discussionmentioning

confidence: 99%

“…In the province of Québec, the prevalence of homozygous FH is approximately 6-fold higher and the minimal estimated frequency of heterozygotes ranges from 1:81 to 1:154 in northeastern Québec. 2 Eleven mutations in the LDL receptor gene are responsible for more than 90% of the heterozygous FH in French Canadian patients, defined on the basis of clinical and biochemical criteria. [3][4][5] Three of those mutations, a deletionϾ15 kb (⌬Ͼ15 kb) at the 5Ј end of the gene and 2 missense mutations in exons 3 (W66G) and 14 (C646Y), are present in approximately 56%, 18%, and 6%, respectively, of FH patients who attend our lipid clinic in Québec city.…”

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confidence: 99%

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Association of Specific LDL Receptor Gene Mutations With Differential Plasma Lipoprotein Response to Simvastatin in Young French Canadians With Heterozygous Familial Hypercholesterolemia

Couture

Brun

Szots

et al. 1998

ATVB

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Abstract-In familial hypercholesterolemia (FH), the efficacy of the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase shows considerable interindividual variation, and several genetic and environmental factors can contribute to explaining this variability. A randomized, double-blind, placebo-controlled clinical trial with simvastatin, an HMG-CoA reductase inhibitor, was conducted in 63 children and adolescents with heterozygous FH. The patients were grouped according to known LDL receptor genotype. After 6 weeks of treatment with 20 mg/d simvastatin, the mean reduction in plasma LDL cholesterol in patients with the W66G mutation (nϭ14) was 31%, whereas in the deletionϾ15 kb (nϭ23) and the C646Y mutation groups (nϭ10), it was 38% and 42%, respectively (PϽ0.05). After treatment with simvastatin, HDL cholesterol levels were increased in all groups, and triglyceride concentrations were significantly reduced. Multiple regression analyses suggested that 42% of the variation of the LDL cholesterol response to simvastatin can be attributed to variation in the mutant LDL receptor locus, apolipoprotein E genotype, and body mass index, while 35% of the variation in HDL cholesterol response was explained by sex and baseline HDL cholesterol. These results show that simvastatin was an effective and well-tolerated therapy for 1 Characteristic phenotypic features of the heterozygous FH form are raised plasma LDL cholesterol concentrations, tendinous xanthomatosis, and premature atherosclerotic coronary artery disease, usually occurring between the ages of 35 and 55 years. Homozygous or compound heterozygous patients show a 6-fold to 8-fold increase in plasma LDL cholesterol concentration and typically present manifestations of coronary artery disease before the age of 20 years.FH is also one of the most common inherited metabolic disorders, with a worldwide frequency of 1 in 500 for heterozygotes and 1 per million for homozygotes. In the province of Québec, the prevalence of homozygous FH is approximately 6-fold higher and the minimal estimated frequency of heterozygotes ranges from 1:81 to 1:154 in northeastern Québec.2 Eleven mutations in the LDL receptor gene are responsible for more than 90% of the heterozygous FH in French Canadian patients, defined on the basis of clinical and biochemical criteria. 3-5 Three of those mutations, a deletionϾ15 kb (⌬Ͼ15 kb) at the 5Ј end of the gene and 2 missense mutations in exons 3 (W66G) and 14 (C646Y), are present in approximately 56%, 18%, and 6%, respectively, of FH patients who attend our lipid clinic in Québec city. The ⌬Ͼ15 kb is a class I mutation and fails to produce immunoprecipitable LDL receptor protein.6,7 The C646Y mutation causes the mutant receptor to be rapidly degraded (class IIA) and results in very low receptor activity (Ͻ2% of normal receptor activity), while the W66G mutation exhibits decreased affinity for lipoprotein ligands (class III) and expresses about 25% of normal receptor activity. 6,8 The founder basis for the high prevalence of these ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Association of Specific LDL Receptor Gene Mutations With Differential Plasma Lipoprotein Response to Simvastatin in Young French Canadians With Heterozygous Familial Hypercholesterolemia

Couture

Brun

Szots

et al. 1998

ATVB

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“…A nationwide FH screening program among patients who were referred to the molecular diagnostic laboratory of the Academic Medical Center in the Netherlands reported that the frequency of HoFH was 1/300,000 based on a genetic test, and the calculated frequency of HeFH was 1/244 12) . Higher heterozygous frequencies ranging from 1/400 to 1/67 were also found in the Finns, French Canadians, Indians in South Africa, Christian Lebanese, and Afrikaners in South Africa, which may result from the founder effect [13][14][15][16][17][18][19] . Increasing efforts have been focused on early detection and earlier treatment of FH patients worldwide.…”

Section: Frequency Of Fh In Asian Populationsmentioning

confidence: 99%

Familial Hypercholesterolemia in Asian Populations

Zhou

Zhao

2016

J Atheroscler Thromb

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Familial hypercholesterolemia (FH) is the most common autosomal disorder characterized by an elevated low-density lipoprotein-cholesterol level and a high risk of premature cardiovascular disease. In this review, we summarize information on FH studies in Asian countries, focusing on mean cholesterol level, FH frequency, diagnostic criteria, genotypes, and clinical care of FH patients in Asian populations. Compared with Western countries, most Asian countries had lower mean cholesterol levels, with a significant variation between different countries. In the limited studies reported, a frequency of 1/900 was reported in Hokuriku district, Japan in 1977 and a frequency of 1/85 among Christian Lebanese in 1979. Recently, a population study in China reported frequencies of 0.47% and 0.28%. However, the different FH frequencies reported were based on different diagnostic criteria. Of 28 publications from 16 Asian countries or regions, 14 used self-defined FH criteria. Only one specific guideline for FH was available, which was developed by Japanese scientists. Six Asian countries joined the Make Early Diagnosis to Prevent Early Deaths program in the late 1990s, and the estimated diagnosis rates of FH ranged from 3% to 10% in these countries. A more recent study explored the awareness, knowledge, and perception of FH among practitioners in Japan, Korea, and Taiwan. The study found that the correct rates of these FH-related questions were low and concluded that lack of country-specific criteria and guidelines may contribute to the lack of FH knowledge in the present survey. More attention and resources should be focused on raising awareness, improving care, and increasing FH research in Asian populations. J Atheroscler Thromb, 2016; 23: 539-549.

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“…Analyzer CX7 (Beckman Instruments, Fullerton, CA, USA) and plasma apoB concentration was assessed by nephelometry (28). Serum creatinine was measured using the kinetic Jaffe reaction method (Beckman Instruments, Fullerton, CA, USA).…”

Section: Subjects and Clinical Datamentioning

confidence: 99%

adiponectine, un modulateur du risque de maladie coronarienne athérosclérotique dans l'hypercholestérolémie familiale /

Bouhali¹

2006

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Homozygous familial hypercholesterolemia among French Canadians in Québec Province.

Cited by 162 publications

References 26 publications

Association of Specific LDL Receptor Gene Mutations With Differential Plasma Lipoprotein Response to Simvastatin in Young French Canadians With Heterozygous Familial Hypercholesterolemia

Association of Specific LDL Receptor Gene Mutations With Differential Plasma Lipoprotein Response to Simvastatin in Young French Canadians With Heterozygous Familial Hypercholesterolemia

Familial Hypercholesterolemia in Asian Populations

adiponectine, un modulateur du risque de maladie coronarienne athérosclérotique dans l'hypercholestérolémie familiale /

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