The molecular basis of familial hypercholesterolaemia in Turkish patients

Sozen, Mert; Whittall, Ros; Öner, Cihan; Tokatlı, Ayşegül; Kalkanoğlu, H. Serap; Dursun, Ali; Coşkun, Turgay; Öner, Reyhan; Humphries, Steve E.

doi:10.1016/j.atherosclerosis.2004.12.042

Cited by 39 publications

(29 citation statements)

References 39 publications

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“…In most countries in Europe in 3-5% of patients the hypercholesterolemia is caused by a single mutation in the gene for ApoB [20]. The R3500Q mutation could not be found in Lebanon [21], Russia [22] and Turkey [23].…”

Section: Discussionmentioning

confidence: 94%

Molecular Characterization of Iranian Patients with Possible Familial Hypercholesterolemia

et al. 2011

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Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipoprotein metabolism caused mainly by mutations in the low-density lipoprotein receptor (LDLR) and apolipoprotein B 100 (APOB) genes. Until now, the molecular basis of FH has been demonstrated in detail in many populations, but there is still very limited Molecular data concerning FH in Iran. The aim of this study was to characterize the LDLR and APOB gene mutations in an Iranian population. A total of 30 non-related Iranian possible FH subjects were studied. Diagnosis of FH was based on the Dutch Lipid Clinic Network diagnostic criteria. All samples were initially tested for three common APOB gene mutations including R3500Q, R3500 W and R3531C using PCR-RFLP assay. Subsequently, promoter and coding region of the LDLR gene was screened by PCR-SSCP analysis and positive results were confirmed by DNA sequencing. Four previously reported polymorphisms 1413G [ A, 1725C [ T, 1773T [ C and 2140 ? 5G [ A were found in *17% (5/30) of population studied.Moreover, no variation was found in APOB gene. Our data indicated that LDLR and APOB gene mutations have not contribution to possible FH in Iranian population studied here. However, we examined three common APOB mutations and LDLR in only 30 patients, and to determine the role of these genes in developing FH in Iran, more FH samples and populations needed to be investigated for the mutations of the related genes.

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Section: Discussionmentioning

confidence: 94%

Molecular Characterization of Iranian Patients with Possible Familial Hypercholesterolemia

et al. 2011

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“…All of them were screened for mutations in the LDLR and ApoB genes, and 123 and 30 FH patients were found to have a mutation in the LDLR and ApoB genes, respectively. A total of 29 pediatric FH patients with mutations in the LDLR gene were found in 36 clinically diagnosed patients in Turkey, and no patients with the R3500Q mutation in the ApoB gene were found 40) . In all, 30 unrelated possible FH subjects diagnosed by the DLCN criteria were tested for mutations in the LDLR and ApoB genes in Iran 41) .…”

Section: Genotypes Of Fh Reported 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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“…We found 11 additional mutations ( Table 2) that were detected by resequencing in known disease-related genes in affected patients (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). These uORF-altering mutations were not present in population controls (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42), and were either the sole mutation detected in the sequenced exons, or were compound heterozygous with a missense/nonsense mutation ( Table 2). The patient presentation was consistent with a recessive phenotype in 3 of the 4 compound heterozygous cases (37, 38, 42, 43), and was ambiguous …”

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confidence: 97%

Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans

Calvo

Pagliarini

Mootha

2009

Proc. Natl. Acad. Sci. U.S.A.

798

899

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Upstream ORFs (uORFs) are mRNA elements defined by a start codon in the 5 UTR that is out-of-frame with the main coding sequence. Although uORFs are present in approximately half of human and mouse transcripts, no study has investigated their global impact on protein expression. Here, we report that uORFs correlate with significantly reduced protein expression of the downstream ORF, based on analysis of 11,649 matched mRNA and protein measurements from 4 published mammalian studies. Using reporter constructs to test 25 selected uORFs, we estimate that uORFs typically reduce protein expression by 30 -80%, with a modest impact on mRNA levels. We additionally identify polymorphisms that alter uORF presence in 509 human genes. Finally, we report that 5 uORF-altering mutations, detected within genes previously linked to human diseases, dramatically silence expression of the downstream protein. Together, our results suggest that uORFs influence the protein expression of thousands of mammalian genes and that variation in these elements can influence human phenotype and disease.polymorphism ͉ post-transcriptional control ͉ proteomics ͉ translation ͉ uORF

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The molecular basis of familial hypercholesterolaemia in Turkish patients

Cited by 39 publications

References 39 publications

Molecular Characterization of Iranian Patients with Possible Familial Hypercholesterolemia

Molecular Characterization of Iranian Patients with Possible Familial Hypercholesterolemia

Familial Hypercholesterolemia in Asian Populations

Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans

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