Update of Japanese common LDLR gene mutations and their phenotypes: Mild type mutation L547V might predominate in the Japanese population

Miyake, Yuka; Yamamura, Taku; Sakai, Naohiko; Miyata, Toshiyuki; Kokubo, Yoshihiro; Yamamoto, Akira

doi:10.1016/j.atherosclerosis.2008.07.005

Cited by 32 publications

(29 citation statements)

References 32 publications

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“…The overall mutation detection rate in our sample is relatively low compared with other similar published cohorts. (40)(41)(42), although similar mutation detection rates were recently reported in Korea (43). This may be because our inclusion criteria were less stringent than in other studies resulting in fewer "monogenic" FH patients and a lower mutation detection rate, and exclusion of those with LDL-C below the diagnostic threshold of 4.5mmol/l increased the mutation detection rate to 46%.…”

Section: Polygenic Familial Hypercholesterolaemiasupporting

confidence: 83%

Molecular genetics of familial hypercholesterolemia in Israel – revisited

Ronen

Ibe²,

Shoshi³

et al. 2017

Atherosclerosis

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Objective: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the genes for LDL receptor (LDLR), apolipoprotein B (APOB) and Proprotein convertase subtilisin/kexin type9 (PCSK9). The purpose of the current investigation was to define the current spectrum of mutations causing FH in Israel. with this being a "mild" FH-causing variant. A significantly higher 6-SNP LDL-C score was found in mutation-negative cases compared with a normal Caucasian cohort (p=0.03), confirming that polygenic inheritance of common LDL-C raising SNPs can produce an FH phenocopy. Methods Conclusions:The results indicate a different spectrum of genetic causes of FH from that found previously, in concordance with the heterogeneous and changing origins of the Israeli population, and confirm that a polygenic cause is also contributing to the FH phenotype in Israel.

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Section: Polygenic Familial Hypercholesterolaemiasupporting

confidence: 83%

Molecular genetics of familial hypercholesterolemia in Israel – revisited

Ronen

Ibe²,

Shoshi³

et al. 2017

Atherosclerosis

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“…On the basis of the data reported thus far, it is difficult to determine whether there are any hot spots of mutations in Koreans. LDLR mutations reported in Koreans have shown little similarities with those reported in other Asian countries such as Japan 24) or Taiwan 25,26) . study 6) , the mean LDL-C level was higher than the levels in the abovementioned study 5) .…”

Section: Genetic Characteristicsmentioning

confidence: 84%

Characteristics and Vascular Complications of Familial Hypercholesterolemia in Korea

Lee

2016

JAT

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“…As for another missense variant, p.Arg115His, the allele frequency in 2KJPN was 0.0039, which was greater than expected for causative variants of FH based on the estimated prevalence of 1 in 200-500 in Japan, hence suggesting that these variants are benign or have mild effects. These two variants showed a higher allele frequency in 2KJPN than that of EAs (p < 0.00001), and both of them were originally reported from domestic studies [63,64]. Thus, these variants could be classified as benign evaluated solely from the viewpoint of their relatively high frequencies.…”

Section: Ldlrmentioning

confidence: 90%

“…Since p.Ser668Arg and p.Trp428* were reported to be causative variants for low LDL cholesterol [63], we considered the other four missense variants (p.Glu54Ala, p.Arg104Cys, p.Arg215His, and p.Ala514Thr) as causative variants for hypercholesterolemia. The population frequency of the causative variants responsible for hypercholesterolemia in PCSK9 was estimated to be 0.001 in 2KJPN, which was based on the allele frequencies of the four responsible variants, all of which were singletons.…”

Section: Pcsk9mentioning

confidence: 99%

Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals

et al. 2017

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Clarifying allele frequencies of disease-related genetic variants in a population is important in genomic medicine; however, such data is not yet available for the Japanese population. To estimate frequencies of actionable pathogenic variants in the Japanese population, we examined the reported pathological variants in genes recommended by the American College of Medical Genetics and Genomics (ACMG) in our reference panel of genomic variations, 2KJPN, which was created by whole-genome sequencing of 2049 individuals of the resident cohort of the Tohoku Medical Megabank Project. We searched for pathogenic variants in 2KJPN for 57 autosomal ACMG-recommended genes responsible for 26 diseases and then examined their frequencies. By referring to public databases of pathogenic variations, we identified 143 reported pathogenic variants in 2KJPN for the 57 ACMG recommended genes based on a classification system. At the individual level, 21% of the individuals were found to have at least one reported pathogenic allele. We then conducted a literature survey to review the variants and to check for evidence of pathogenicity. Our results suggest that a substantial number of people have reported pathogenic alleles for the ACMG genes, and reviewing variants is indispensable for constructing the information infrastructure of genomic medicine for the Japanese population.

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Update of Japanese common LDLR gene mutations and their phenotypes: Mild type mutation L547V might predominate in the Japanese population

Cited by 32 publications

References 32 publications

Molecular genetics of familial hypercholesterolemia in Israel – revisited

Molecular genetics of familial hypercholesterolemia in Israel – revisited

Characteristics and Vascular Complications of Familial Hypercholesterolemia in Korea

Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals

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