Association between polymorphisms in the APOB gene and hyperlipidemia in the Chinese Yugur population

Ql, Gu; Han, Yaling; Ym, Lan; Y, Li; W, Kou; Ys, Zhou; Xj, Hai; Yan, Bin; Ch, Ci

doi:10.1590/1414-431x20176613

Cited by 18 publications

(24 citation statements)

References 30 publications

(30 reference statements)

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“…p.12_15del is associated with higher levels of apoB and LDL cholesterol without affecting triglyceride levels 36,37) . p.N2785H has no effect on hyperlipidemia risk in the Chinese population 37) . No diseasecausing variants were detected in the apo B gene.…”

Section: Discussionmentioning

confidence: 99%

Variants of Lipid-Related Genes in Adult Japanese Patients with Severe Hypertriglyceridemia

Matsunaga

Nagashima

Yamagishi

et al. 2020

JAT

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Hypertriglyceridemia is a type of dyslipidemia that contributes to atherosclerosis and coronary heart disease. Variants in lipoprotein lipase (LPL), apolipoprotein CII (APOC2), apolipoprotein AV (APOA5), glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), lipase maturation factor 1 (LMF1), and glucokinase regulator (GCKR) are responsible for hypertriglyceridemia. We investigated the molecular basis of severe hypertriglyceridemia in adult patients referred to the Clinical Laboratory at Fukuoka University Hospital. Methods: Twenty-three adult patients with severe hypertriglyceridemia (1,000 mg/dL, 11.29 mmol/L) were selected. The coding regions of candidate genes were sequenced by next-generation sequencing. Forty-nine genes reportedly associated with hypertriglyceridemia were analyzed. Results: In the 23 patients, we detected 70 variants: 28 rare and 42 common ones. Among the 28 rare variants with 1% allele frequency, p.I4533L in APOB, p.M490I in MLXIPL, p.L152M in NCAN, and p.S264T in TIMD4 were novel. We did not observe single gene homozygous or compound heterozygous disease-causing rare variants in any of the 23 hypertriglyceridemia cases. However, in silico algorithms and previous reports indicated that five rare variants, APOA5 (p.T184S), GCKR (c.354 1G A), LMF1 (p.G410R), and LRP1 (p.G813R; p.R2173Q), and seven common variants, APOA5 (pG185C), APOE (p.C130R; p.E262K/p.E263K), GCKR (p.V103M), GPIHBP1 (p.C14F), LRP1 (p.Y4054F), and MLXIPL (p.Q241H), can cause hypertriglyceridemia. However, all five disease-causing rare variants detected in this study were heterozygous. Conclusions: The prevalence of disease-causing rare variants in candidate genes in severe hypertriglyceridemia patients was low. The major causes of severe hypertriglyceridemia were not single gene abnormalities, but involved multiple gene variations and environmental factors. ciency, thyroid disease, and chemotherapy. Plasma TG is largely contained in TG-rich lipoproteins, such as very low-density lipoprotein (VLDL) and chylomicron particles. Lipoprotein lipase (LPL) is a critical enzyme in determining plasma triglyceride levels and LPL variants can result in severe hypertriglyceridemia. Moreover, apoprotein (apo)A-V, apoC-II, glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1), and lipase maturation factor 1 (LMF1) are also co-factors involved in the activation, transportation, or matura-Copyright©2020 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

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Section: Discussionmentioning

confidence: 99%

Variants of Lipid-Related Genes in Adult Japanese Patients with Severe Hypertriglyceridemia

Matsunaga

Nagashima

Yamagishi

et al. 2020

JAT

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“…8,9 Studies have confirmed that multiple singlenucleotide polymorphisms (SNPs) in APOB are associated with dyslipidemia. 10,11 China is a multiethnic country comprising Han Chinese, which accounts for the majority, and 55 ethnic minorities. The Maonan ethnic group is one of the ethnic minorities living in the mountainous region, which has a small population.…”

Section: Introductionmentioning

confidence: 99%

Correlation Between the APOB rs1042034 SNP and Blood Lipid Characteristics of 2 Ethnic Groups in China

Zhang

Yin

Yao

et al. 2019

Clin Appl Thromb Hemost

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The apolipoprotein (Apo) B gene (APOB) is a susceptible gene for dyslipidemia. The purpose of this investigation was to explore the relationship between the APOB rs1042034 single-nucleotide polymorphism (SNP) and serum lipid levels in the Maonan and Han populations. A total of 598 Maonan participants and 609 Han participants were genotyped by polymerase chain reaction and restriction fragment length polymorphism, and the genotypes were also verified by sequencing. There were no differences in genotype and allele frequencies between the 2 ethnic groups or between males and females. The levels of triglyceride (TG) in Maonans were higher and high-density lipoprotein cholesterol was lower in the A allele carriers than the A allele noncarriers; the A allele carriers in Hans had higher TG levels and lower ApoA1/ApoB ratio than the A allele noncarriers (P < .05 for all). Subgroup analysis showed that the A allele carriers in Maonan females had higher TG levels and the A allele carriers in Han females had higher TG levels and lower ApoA1/ApoB ratio than the A allele noncarriers (P < .05 for all). In our study populations, there may be ethnicity-and/or sex-specific associations between the APOB rs1042034 SNP and serum lipid levels.

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“…APOB is considered the third most relevant candidate modifier gene for MEND syndrome because up to seven of its allelic variants have been reported to be significantly associated with increased levels of LDL‐C or hyperlipidemia. Among these variants, p.Ala618Val (rs679899) (Gu et al, ) and p.Ile408Thr (rs12714225) (Teslovich et al, ) were the fourth and fifth top variants in Table , respectively. The presence of p.Ala618Val in compound heterozygosity with p.Ile408Thr in Patients 1, 2, and 3 and the absence of both in Patient 4, who had the mildest MEND phenotype, supports its contribution to the genotype–phenotype association in MEND syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, all patients with MEND syndrome appear to have a basal deficiency in APOB function because they carry APOB alleles carrying ancestral sequences of the SNPs rs1042034 and rs676210. These SNPs are hypothesized to predispose middle‐aged and elderly members of the Chinese Yugur population to hyperlipidemia in combination with other genetic or nutritional factors (Gu et al, ). Patient 2 and especially Patient 3 may exhibit somewhat higher degrees of deficiency in the synthesis of lipoproteins because of the presence of compound heterozygosity for potentially functional APOB alleles.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic severity in a family with MEND syndrome is directly associated with the accumulation of potentially functional variants of cholesterol homeostasis genes

Barboza-Cerda

Barboza-Quintana

Martínez-Aldape

et al. 2019

Molec Gen & Gen Med

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Background Male EBP disorder with neurologic defects (MEND) syndrome is an X‐linked disease caused by hypomorphic mutations in the EBP (emopamil‐binding protein) gene. Modifier genes may explain the clinical variability among individuals who share a primary mutation. Methods We studied four males (Patient 1 to Patient 4) exhibiting a descending degree of phenotypic severity from a family with MEND syndrome. To identify candidate modifier genes that explain the phenotypic variability, variants of homeostasis cholesterol genes identified by whole‐exome sequencing (WES) were ranked according to the predicted magnitude of their effect through an in‐house scoring system. Results Twenty‐seven from 105 missense variants found in 45 genes of the four exomes were considered significant (−5 to −9 scores). We found a direct genotype–phenotype association based on the differential accumulation of potentially functional gene variants among males. Patient 1 exhibited 17 variants, both Patients 2 and 3 exhibited nine variants, and Patient 4 exhibited only five variants. Conclusion We conclude that APOA5 (rs3135506), ABCA1 (rs9282541), and APOB (rs679899 and rs12714225) are the most relevant candidate modifier genes in this family. Relative accumulation of the deficiencies associated with variants of these genes along with other lesser deficiencies in other genes appears to explain the variable expressivity in MEND syndrome.

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Association between polymorphisms in the APOB gene and hyperlipidemia in the Chinese Yugur population

Cited by 18 publications

References 30 publications

Variants of Lipid-Related Genes in Adult Japanese Patients with Severe Hypertriglyceridemia

Variants of Lipid-Related Genes in Adult Japanese Patients with Severe Hypertriglyceridemia

Correlation Between the APOB rs1042034 SNP and Blood Lipid Characteristics of 2 Ethnic Groups in China

Phenotypic severity in a family with MEND syndrome is directly associated with the accumulation of potentially functional variants of cholesterol homeostasis genes

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