Complex genetic contribution of the Apo AI-CIII-AIV gene cluster to familial combined hyperlipidemia. Identification of different susceptibility haplotypes.

Dallinga‐Thie, Geesje M.; Trip, M. Van Linde-Sibenius; Rotter, Jerome I.; Cantor, Rita M.; Bu, Xingyao; Lusis, Aldons J.; Bruin, T.W.A. de

doi:10.1172/jci119260

Cited by 102 publications

(93 citation statements)

References 43 publications

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“…The biochemical basis for the association of G allele with hypertriglyceridemia has yet to be established. Dallinga-Thie et al (25,26) and Shoulders et al (27,28) reported an association between levels of apo-CIII and G allele. The Sst I polymorphism is located in the 3'untranslated region of apo-CIII gene.…”

Section: Resultsmentioning

confidence: 96%

Apolipoprotein CIII polymorphism and triglyceride levels of a Japanese population living in Southern Brazil

Parzianello

Oliveira

Coelho

2008

Braz J Med Biol Res

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Apolipoprotein CIII (apo-CIII) participates in the regulation of triglyceride-rich lipoprotein metabolism. Several polymorphic sites have been detected within and around the apo-CIII gene. Here, we examined the relationship between apo-CIII Sst I polymorphism (CC, CG, GG genotypes) and plasma triglyceride (TG) levels in a group of 159 Japanese individuals living in Southern Brazil. The sample was divided into a group of Japanese descendants (N = 51) with high TG (HTG; >200 mg/dL) and a group of Japanese descendants (N = 108) with normal TG (NTG; <200 mg/dL). TG and total cholesterol levels were analyzed by an enzymatic method using the Labtest-Diagnostic kit and high-and low-density lipoproteins by a direct method using the Labtest-Diagnostic kit and DiaSys Diagnostic System International kit, respectively. A 428-bp sequence of apo-CIII gene was amplified using oligonucleotide primers 5' GGT GAC CGA TGG CTT CAG TTC CCT GA 3' and 5' CAG AAG GTG GAT AGA GCG CTG GCC T 3'. The PCR products were digested with a restriction endonuclease Sst I. Rare G allele was highly prevalent in our study population (0.416) compared to Caucasians (0.00-0.11). G allele was almost two times more prevalent in the HTG group compared to the NTG group (P < 0.001). The genotype distribution was consistent with the Hardy-Weinberg equilibrium. There was a significant association between rare G allele and HTG in Japanese individuals living in Southern Brazil as indicated by one-way ANOVA, P < 0.05.

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Section: Resultsmentioning

confidence: 96%

Apolipoprotein CIII polymorphism and triglyceride levels of a Japanese population living in Southern Brazil

Parzianello

Oliveira

Coelho

2008

Braz J Med Biol Res

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“…Table-2 (18) and French (Canada) (19) populations. Most of these studies found a relationship between the presence of $2 allele and hypertriglyceridemia (2)(3)(4)(5)(6)9,11,(13)(14)(15)(16)18,(20)(21)(22). An association of this allele with CAD was also reported (26)(27)(28).…”

Section: ) Genotypic Distribution Was In Agreement Withmentioning

confidence: 97%

“…This polymorphism may directly modulate the expression of the APOC3 gene (3). Increased levels of apoCIII has been reported in $2 carders (20)(21)(22)(23). It is possible that this site may be involved in mRNA stability because 3' untranslated sequences have been shown to influence the mRNA turnover (30).…”

Section: -38mentioning

confidence: 99%

“…An Sstl polymorphism resulting from a C->G base transversion in 3' untranslated region of APOC3 gene had been studied extensively in relation to hypertriglyceridemia . Here, the rare $2 allele apparently predisposes an individual to hypertriglyceride mia (2)(3)(4)(5)(6)9,11,(13)(14)(15)(16)18,(20)(21)(22). Asian Indians are reported to have high genetic predisposition to develop CAD.…”

Section: Introductionmentioning

confidence: 99%

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Study of apolipoproteinc3 Sstl polymorphism in healthy volunteers from Northern India

Chhabra

Agarwal²,

Vasisht

et al. 2003

Indian J Clin Biochem

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Several studies including a small case-control (hypertriglyceridemic / normotriglyceridemic individuals) study by us revealed close association between rare $2 allele of APOC3 Sstl polymorphism and hypertriglyceddemia. With the understanding that Asian Indians are highly vulnerable to the adverse effects of hypertdglyceridemia, we extended the investigation and studied the frequency distribution of this polymorphism in 216 healthy volunteers from Northern plains of India. We found that more than 50% of the study population had one ortwo $2 allele. This may suggest that a larger fraction of this population is genetically predisposed to hypertdglyceddemia.

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“…9 -11 One study has proposed more complex models to explain the contribution of A-I/C-III/A-IV to FCHL; these models involve epistatic interactions of specific haplotypes at the locus. 12 The lipoprotein lipase (LPL) gene is also an attractive candidate for FCHL. Decreased activity of LPL in subjects with FCHL has been shown, 13 and positive associations have been reported between FCHL and genetic variants in the LPL promoter and in exon 6.…”

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confidence: 99%

Replication of Linkage of Familial Combined Hyperlipidemia to Chromosome 1q With Additional Heterogeneous Effect of Apolipoprotein A-I/C-III/A-IV Locus

Coon

Myers

Borecki

et al. 2000

ATVB

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Abstract-Familial combined hyperlipidemia (FCHL), the most common familial dyslipidemia, is implicated in up to 20% of cases of premature coronary heart disease. Although underlying mutations for FCHL have yet to be identified, several candidate genes/regions have been identified. A positive linkage to chromosome 1q markers has been reported, with the highest lod score of 5.93 occurring at a location between D1S104 and D1S1677. Using the same diagnostic criteria, the Family Heart Study (FHS) has defined 71 FCHL families, comprising 170 cases, for a total of 137 possible affected sibling pairs. The FCHL criteria require elevation in serum low density lipoprotein cholesterol and triglyceride levels within the family, with at least 2 affected first-degree relatives. Markers D1S104 and D1S1677 were typed, and significant allele sharing was found in FCHL sibships (multipoint lod score with use of the model from the Finnish study was 2.52, and multipoint nonparametric score was 2.48; Pϭ0.007), replicating linkage in this chromosome 1 region. In addition, previously reported linkage of FCHL to apolipoprotein A-I/C-III/A-IV has been investigated in FHS families. FHS results revealed positive but nonsignificant allele sharing among FCHL sibships with apolipoprotein A-I/C-III/ A-IV by use of marker D11S4127 (nonparametric linkage score 1.11, Pϭ0.13). Two-locus analyses of D1S104 and D11S4127 suggested possible heterogeneity rather than epistasis, with a maximum 2-locus lod score of 3.05. A nonparametric 2-locus analysis revealed significant improvement in the 2-locus versus single-locus scores. Key Words: genetic linkage Ⅲ coronary disease Ⅲ hyperlipidemia F amilial combined hyperlipidemia (FCHL) is the most common familial dyslipidemia, with a prevalence of 1% to 2%, 1 and is implicated in up to 20% of cases of premature coronary heart disease (CHD). 2 FCHL criteria require elevation of serum total cholesterol and triglyceride levels within the family, with at least 2 affected first-degree relatives. 3 Studies of the genetics of FCHL have been complicated by uncertain phenotype definition, likely genetic heterogeneity, and unknown mode of inheritance. These difficulties have thus far prevented the identification of underlying mutations for FCHL. Several loci have produced positive results, although often with mixed findings in replication studies.Perhaps the most promising candidate region is on chromosome 1q21-23. Pajukanta et al 4 recently published positive linkage to chromosome 1q markers in 250 individuals (115 affected) from 31 Finnish FCHL families, with the highest lod score of 5.93 occurring between D1S104 and D1S1677.

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Complex genetic contribution of the Apo AI-CIII-AIV gene cluster to familial combined hyperlipidemia. Identification of different susceptibility haplotypes.

Cited by 102 publications

References 43 publications

Apolipoprotein CIII polymorphism and triglyceride levels of a Japanese population living in Southern Brazil

Apolipoprotein CIII polymorphism and triglyceride levels of a Japanese population living in Southern Brazil

Study of apolipoproteinc3 Sstl polymorphism in healthy volunteers from Northern India

Replication of Linkage of Familial Combined Hyperlipidemia to Chromosome 1q With Additional Heterogeneous Effect of Apolipoprotein A-I/C-III/A-IV Locus

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