NewMspI polymorphism at +83 bp of the human apolipoprotein al gene: Association with increased circulating high density lipoprotein cholesterol levels

Wang, X.L.; Badenhop, Renee F.; Humphrey, Karen E.; Wilcken, D. E. L.

doi:10.1002/(sici)1098-2272(1996)13:1<1::aid-gepi1>3.0.co;2-d

Cited by 54 publications

(52 citation statements)

References 18 publications

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“…Whereas one might have supposed that the allele frequencies would be lower in the coronary population if these genotypes conferred a degree of protection, i.e. associated with an elevated HDL-C, the allele frequencies were not statistically different from the frequencies we have found in a healthy population (22). That the genotypes were not associated with elevated HDL-C and apo AI is perhaps not surprising consid- The observed numbers of cases and the column percentages (in brackets) are presented.…”

Section: Discussioncontrasting

confidence: 88%

“…Both base changes are at regulatory hot spots (29-32). The base change at Ϫ75 bp (MspI1 polymorphism) is known to be associated with altered apo AI transcription (16,33,34) and it is possible that the base change at ϩ83 bp (MspI2 polymorphism) also alters either transcription or translation although this has not yet been established (22). One could postulate that their association is with altered apo AI gene expression such that there is altered susceptibility to the effects of environmental influences.…”

Section: Discussionmentioning

confidence: 99%

“…The association between the base substitution at Ϫ 75 bp and HDL-C levels are also reported to be influenced by gender (12,13) and smoking (12,20). More recently, we have shown that C → T and/or G → A transitions at ϩ 83 bp and/or ϩ 84 bp of the apo AI gene are also associated with increased HDL-C levels (21,22). Whilst the frequency in a healthy population of the ϩ 83 bp substitution was less common (rare allele frequency: 0.041) than that at Ϫ 75 bp (rare allele frequency: 0.221), the base substitution at ϩ 83 bp was associated with a much greater elevation in circulating HDL-C level (22).…”

Section: Introductionmentioning

confidence: 88%

“…More recently, we have shown that C → T and/or G → A transitions at ϩ 83 bp and/or ϩ 84 bp of the apo AI gene are also associated with increased HDL-C levels (21,22). Whilst the frequency in a healthy population of the ϩ 83 bp substitution was less common (rare allele frequency: 0.041) than that at Ϫ 75 bp (rare allele frequency: 0.221), the base substitution at ϩ 83 bp was associated with a much greater elevation in circulating HDL-C level (22). Both base substitutions result in loss of MspI restriction sites so that both polymorphic markers can be detected with a single PCR and a single MspI digestion (22).…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms at the 5'-end of the apolipoprotein AI gene and severity of coronary artery disease.

Wang¹,

Liu²,

McCredie³

et al. 1996

J. Clin. Invest.

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Elevated HDL-cholesterol (C) and apo AI are associated with decreased coronary artery disease (CAD) risk. We determined distributions of two MspI polymorphisms of the apo AI gene, associated in other studies with increased HDL-C, among 644 patients aged Յ 65 years in relation to circulating lipids and CAD severity assessed angiographically. The rare allele distributions at both sites were in Hardy-Weinberg equilibrium in these patients but the base changes were not associated with HDL-C and apo AI levels.

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Section: Discussioncontrasting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Polymorphisms at the 5'-end of the apolipoprotein AI gene and severity of coronary artery disease.

Wang¹,

Liu²,

McCredie³

et al. 1996

J. Clin. Invest.

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“…24 The positions Ϫ482 and Ϫ455 of the promoter region of the APOC3 gene were screened for 2 frequently occurring point mutations. 41 Two MspI sites at positions Ϫ75 and ϩ83 in the APOA1 gene, 42 which is located downstream of the SstI polymorphism, were screened to perform haplotyping.…”

Section: Molecular Analyses Of Candidate Genesmentioning

confidence: 99%

Severe Hyperlipidemia in Apolipoprotein E2 Homozygotes Due to a Combined Effect of Hyperinsulinemia and an Sst I Polymorphism

Sijbrands

Hoffer

Meinders

et al. 1999

ATVB

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Abstract-More than 90% of patients with type III hyperlipoproteinemia are homozygous carriers of the apolipoprotein (apo) E*2 allele. The great majority of these apoE2(Arg1583 Cys) homozygotes in the general population, however, are normolipidemic. Apparently, expression of the hyperlipidemic state requires additional genetic and/or environmental factors, suggesting a multifactorial etiology. To elucidate these additional risk factors, we analyzed normolipidemic and hyperlipidemic apoE2 homozygotes. Hyperinsulinemia was observed in 27 of 49 apoE2 homozygotes and associated with elevated lipid levels: hyperinsulinemic apoE2 homozygotes had type III hyperlipoproteinemia 6 times more often than apoE2 homozygotes with normal insulin levels (odds ratio 6.2, Pϭ0.02). We screened the normolipidemic and hyperlipidemic apoE2 homozygotes for common variants in candidate genes involved in lipolysis-the APOA1-C3-A4 gene cluster, lipoprotein lipase, and hepatic lipase-and analyzed for associations with the expression of hyperlipidemia.In the hyperinsulinemic group, the 7 carriers of the SstI polymorphism (S2) in the APOC3 gene displayed severely elevated VLDL cholesterol (P insulin by SstI Ͻ0.001) and VLDL triglyceride (P insulin by SstI Ͻ0.01) and low levels of HDL (P insulin by SstI Ͻ0.02). In the normoinsulinemic group, no such relation of the SstI polymorphism with hyperlipidemia was observed. These data provide the first evidence for a combined effect of hyperinsulinemia and the SstI polymorphism on the expression of hyperlipidemia in apoE2 homozygotes. (HLP), is characterized by dysfunctional apolipoprotein (apo) E and by increased serum concentrations of both cholesterol and triglyceride. 3 Biochemically, the disorder is characterized by the presence of ␤-VLDL particles, which are cholesterol-enriched chylomicron and VLDL remnants. More than 90% of the patients with type III HLP are homozygous for a specific isoform of apoE: apoE2(Arg1583 Cys). 4 Compared with the other common isoforms, apoE3 and E4, apoE2 has Ͻ2% binding activity for hepatic lipoprotein receptors, 5,6 which renders apoE2 homozygotes susceptible to accumulation of circulating remnant lipoprotein particles. However, the majority of apoE2 homozygotes in the general population are normolipidemic or even hypolipidemic. 7,8 The latter is due to low plasma LDL levels as a result of (1) compensatory upregulated expression of LDL receptors on the surface of hepatocytes to maintain a normal intrahepatocellular cholesterol concentration and (2) a delayed conversion of IDL into LDL in plasma. 9 The expression of overt hyperlipidemia in apoE2 homozygotes occurs despite compensatory mechanisms, when additional genetic and/or environmental factors result in large amounts of circulating remnants. 4 For the majority of the apoE2 homozygotes with type III HLP, the additional factors causing hyperlipidemia are not known. It has been reported that uncontrolled diabetes mellitus 10,11 and hypothyroidism 12 occasionally contribute to the expression of type III HLP in apo...

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Genetic association of five apolipoprotein polymorphisms with serum lipoprotein-lipid levels in African blacks

Kamboh¹,

Bunker²,

Aston³

et al. 1999

Genet. Epidemiol.

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Genetic studies carried out mainly in European and European‐derived populations have shown that common polymorphisms in genes coding for apolipoproteins are significant determinants of serum lipoprotein‐lipid levels variation. However, except for a few sporadic studies, the distribution of apolipoprotein polymorphisms and their association with serum lipoprotein‐lipid levels have not been evaluated systematically in African or African‐derived populations. In this investigation we have studied five apolipoprotein polymorphisms, including APOA1/MspI –75 bp, APOA1/MspI +83 bp, APOC3/PvuII, APOE, and APOH in 786 Africans (493 men, 293 women) from Nigeria. The sample is comprised of Nigerian civil servants consisting of 462 junior staff (less affluent) and 324 senior staff (more affluent) where staff status is a correlate of their socioeconomic status. We first examined genetic associations in the total sample stratified by gender to determine the role of apolipoprotein polymorphisms in affecting serum lipid profile in the general population, and then by staff status to evaluate possible gene‐environment interactions. In the total sample, the APOC3/PvuII polymorphism showed significant effect on HDL‐cholesterol (P = 0.029) and HDL3‐cholesterol (P = 0.009) in women, and the APOE polymorphism was significantly associated with total cholesterol (P = 0.031) and LDL‐cholesterol (P = 0.0006) in women. Multiple regression analyses showed that the APOC3/PvuII polymorphism accounts for about 2 and 3% of the variation in HDL‐cholesterol and HDL3‐cholesterol, respectively, in women; while the APOE polymorphism accounted for about 5 and 6% of the variation in total‐ and LDL‐cholesterol, respectively, in women. Whereas the association of the APOE polymorphism was independent of the staff status, the significant affect of the APOC3/PvuII polymorphism on HDL‐ and HDL3‐cholesterol was confined to senior staff women where it explained about 7% of their variation. We also observed an interaction between staff and the APOH polymorphism in affecting cholesterol levels. The APOH polymorphism showed significant association with total cholesterol (P = 0.010) and LDL‐cholesterol (P = 0.016) in senior staff women and explained about 7 and 5% of their phenotypic variations, respectively. These data indicate that gene‐environment interaction may play an important role in affecting serum lipid profile in African populations. Genet. Epidemiol. 16:205–222, 1999. © 1999 Wiley‐Liss, Inc.

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NewMspI polymorphism at +83 bp of the human apolipoprotein al gene: Association with increased circulating high density lipoprotein cholesterol levels

Cited by 54 publications

References 18 publications

Polymorphisms at the 5'-end of the apolipoprotein AI gene and severity of coronary artery disease.

Polymorphisms at the 5'-end of the apolipoprotein AI gene and severity of coronary artery disease.

Severe Hyperlipidemia in Apolipoprotein E2 Homozygotes Due to a Combined Effect of Hyperinsulinemia and an Sst I Polymorphism

Genetic association of five apolipoprotein polymorphisms with serum lipoprotein-lipid levels in African blacks

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