A novel single base deletion in the LDLR gene (211delG): Effect on serum lipid profiles and the influence of other genetic polymorphisms in the ACE, APOE and APOB genes

Ward, Alana; O’Kane, Maurice; Nicholls, D. P.; Nevin, N. C.; Graham, Colin A.

doi:10.1016/0021-9150(95)05685-8

Cited by 31 publications

(17 citation statements)

References 24 publications

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“…When LDL-cholesterol concentrations are the only clinical phenotype, however, it is not possible to make unequivocal diagnoses among family members of the index case by means of cholesterol measurements (31)(32)(33)(34). The use of DNA arrays to identify FH-causing mutations could allow reliable early diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Reliable Low-Density DNA Array Based on Allele-Specific Probes for Detection of 118 Mutations Causing Familial Hypercholesterolemia

Tejedor

Castillo²,

Mozas³

et al. 2005

Clinical Chemistry

116

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Background: Patients with familial hypercholesterolemia (FH) have a high risk of premature cardiovascular disease (PCVD). Mutations in the LDL receptor (LDLR)gene and the R3500Q mutation in the apolipoprotein B (APOB) gene are known to cause FH, but lack of high-throughput methods makes routine genetic diagnosis difficult. The objective of this work was to develop a DNA array for large-scale identification of mutant LDLR alleles. Methods: We developed a low-density oligonucleotide microarray to identify 118 DNA sequence variations (117 for the LDLR gene and 1 for the APOB gene). We verified specificity and sensitivity by analyzing 1180 previously sequenced DNA samples, and conducted a blind study screening 407 Spanish patients with a clinical diagnosis of FH. Results: The DNA array confirmed the previous genotyping results in almost all cases. In the blind study, the microarray detected at least 1 mutation in 51% of the patients for whom clinical diagnosis was classified as certain according to Dutch FH-MEDPED criteria; it also identified mutations in 37% of those with a diagnosis of probable/possible FH, thus giving a definite diagnosis.

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Section: Discussionmentioning

confidence: 99%

Reliable Low-Density DNA Array Based on Allele-Specific Probes for Detection of 118 Mutations Causing Familial Hypercholesterolemia

Tejedor

Castillo²,

Mozas³

et al. 2005

Clinical Chemistry

116

View full text Add to dashboard Cite

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“…FH is a dominantly inherited disorder, affecting about 1 in 500 of the general population. FH is diagnosed clinically by raised levels of low-density lipoprotein cholesterol (LDL-C), tendon xanthomata (TX), premature CHD, and a family history of hypercholesterolemia and premature CHD [Koivisto et al, 1992;Ward et al, 1996]. Recent advances make it possible to test for common mutations in two genes: the LDL-receptor gene (LDLR), which cause FH, and the apolipoprotein B gene (APOB), which causes a clinically indistinguishable disorder, familial defective apolipoprotein B100 (FDB) [Myant, 1993].…”

Section: Introductionmentioning

confidence: 99%

Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: A randomized controlled trial

Marteau

Senior

Humphries

et al. 2004

American J of Med Genetics Pt A

181

204

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This trial tests the hypothesis that confirming a clinical diagnosis of familial hypercholesterolemia (FH) by finding a genetic mutation reduces patients' perceptions of control over the disease and adherence to risk-reducing behaviors. Three hundred forty-one families, comprising 341 hypercholesterolemia probands and 128 adult relatives, were randomized to one of two groups: (a) routine clinical diagnosis; (b) routine clinical diagnosis plus genetic testing (mutation searching in probands and direct gene testing in relatives). The main outcome measures were perceptions of control over hypercholesterolemia, adherence to cholesterol-lowering medication, diet, physical activity, and smoking. There was no support for the main hypothesis: finding a mutation had no impact on perceived control or adherence to risk-reducing behavior (all P-values > 0.10). While all groups believed that lowering cholesterol was an effective way of reducing the risk of a heart attack, participants in whom a mutation was found believed less strongly in the efficacy of diet in reducing their cholesterol level (P = 0.02 at 6 months) and showed a trend in believing more strongly in the efficacy of cholesterol-lowering medication (P = 0.06 at 6 months). In conclusion, finding a mutation to confirm a clinical diagnosis of FH in a previously aware population does not reduce perceptions of control or adherence to risk-reducing behaviors. The pattern of findings leads to the new hypothesis that genetic testing does not affect the extent to which people feel they have control over a condition, but does affect their perceptions of how control is most effectively achieved. Further work is needed to determine whether similar results will be obtained in populations with little previous awareness of their risks.

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“…However, a genetic test can detect up to 20 percent of affected individuals who would not have been identified using clinical criteria alone (e.g. Ward, O'Kane, Nicholls, Young, Nevin, & Graham, 1996).…”

Section: Introductionmentioning

confidence: 99%

Making Sense of Risk: An Interpretative Phenomenological Analysis of Vulnerability to Heart Disease

et al. 2002

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This study investigates perceptions of familial hypercholesterolaemia (FH) and its genetic basis in patients diagnosed with, and receiving treatment for, FH. Semistructured interviews were conducted with seven patients. Transcripts were analysed using interpretative phenomenological analysis (IPA). Participants reported engaging in an active process of seeking causes for their FH. FH was invariably attributed to genes. In some cases diet and stress were also considered as causes of FH. Causal attributions appear to be both a determinant and a result of behavioural strategies to reduce risk. On the whole, FH was perceived as unproblematic, a perception that appeared to reflect downward social comparison processes. Nonetheless, participants reported acting in ways consonant with the perception of an increased risk of heart attack, in particular, being vigilant to symptoms of a possible heart attack.

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A novel single base deletion in the LDLR gene (211delG): Effect on serum lipid profiles and the influence of other genetic polymorphisms in the ACE, APOE and APOB genes

Cited by 31 publications

References 24 publications

Reliable Low-Density DNA Array Based on Allele-Specific Probes for Detection of 118 Mutations Causing Familial Hypercholesterolemia

Reliable Low-Density DNA Array Based on Allele-Specific Probes for Detection of 118 Mutations Causing Familial Hypercholesterolemia

Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: A randomized controlled trial

Making Sense of Risk: An Interpretative Phenomenological Analysis of Vulnerability to Heart Disease

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