Common and Rare Alleles in Apolipoprotein B Contribute to Plasma Levels of Low-Density Lipoprotein Cholesterol in the General Population

Benn, Marianne; Stene, Maria C. A.; Nordestgaard, Børge G.; Jensen, Gorm; Steffensen, Rolf; Tybjærg‐Hansen, Anne

doi:10.1210/jc.2007-1365

Cited by 38 publications

(37 citation statements)

References 23 publications

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“…APOB SNP rs693 has been associated with increased LDL-C, TC, and APOB levels in the general population (16). Although these associations could not be found in our group of GHD adults, T allele carriers of this polymorphism showed higher serum HDL-C concentrations at baseline.…”

Section: Snpscontrasting

confidence: 73%

“…Common genetic variants in genes involved in the regulation of lipid metabolism might influence the lipid response to GHRT, as suggested in two previous studies (15,29). Therefore, we conducted this study using the candidate gene approach by selecting 20 SNPs in genes well known for their association with serum lipid concentrations in other populations (16,17,18,19,20,21,22,23) and genes related to risk of coronary heart disease (17,19,20) and investigated their contribution to the lipid profile and lipid response to GHRT in GHD adults.…”

Section: Discussionmentioning

confidence: 97%

“…However, it remains unknown whether additional SNPs in genes related to lipid metabolism contribute to variations in the lipid profile of GHD adults as well as to their changes after GHRT. Therefore, our aim was to evaluate whether gene polymorphisms previously shown to influence serum lipid concentrations in other populations (16,17,18,19,20,21,22,23) could have an impact on the lipid profile of GHD adults and influence changes in serum lipid concentrations in response to GHRT.…”

Section: Introductionmentioning

confidence: 99%

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Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy

Barbosa

Glad

Nilsson

et al. 2012

European Journal of Endocrinology

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ObjectiveGH deficiency (GHD) in adults is associated with an altered serum lipid profile that responds to GH replacement therapy (GHRT). This study evaluated the influence of polymorphisms in genes related to lipid metabolism on serum lipid profile before and after 1 year of GHRT in adults.Design and methodsIn 318 GHD patients, total cholesterol (TC) serum concentrations, LDL-C, HDL-C, and triglycerides (TG) were assessed. Using a candidate gene approach, 20 single nucleotide polymorphisms (SNPs) were genotyped. GH dose was individually titrated to obtain normal serum IGF1 concentrations.ResultsAt baseline, the minor alleles of cholesteryl ester transfer protein (CETP) gene SNPs rs708272 and rs1800775 were associated with higher serum TC and apolipoprotein E (APOE) gene SNP rs7412 with lower TC concentrations;CETPSNPs rs708272, rs1800775, and rs3764261 and apolipoprotein B (APOB) gene SNP rs693 with higher serum HDL-C;APOESNP rs7412, peroxisome proliferator-activated receptor gamma (PPARG) gene SNP rs10865710 with lower LDL-C, andCETPSNP rs1800775 with higher LDL-C; andAPOE/C1/C4/C2cluster SNP rs35136575 with lower serum TG. After treatment,APOBSNP rs676210 GG genotype was associated with larger reductions in TC and LDL-C andPPARGSNP rs10865710 CC genotype with greater TC reduction. All associations remained significant when adjusted for age, sex, and BMI.ConclusionsIn GHD adults, multiple SNPs in genes related to lipid metabolism contributed to individual differences in baseline serum lipid profile. The GH treatment response in TC and LDL-C was influenced by polymorphisms in theAPOBandPPARGgenes.

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Section: Snpscontrasting

confidence: 73%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy

Barbosa

Glad

Nilsson

et al. 2012

European Journal of Endocrinology

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“…Hydrolyzing TAG in the ApoB-LP composition HL plays a significant role in their re-modelling in the bloodstream. It is known that the HL activity specifies substantially the lipid composition, size and properties of LDL [43].…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Complexes and Lipoprotein Metabolism – Experience of Grape Extracts Application Under Metabolic Syndrome and Neurogenic Stress

Zagayko¹,

Kravchenko²,

Krasilnikova³

2012

Lipoproteins - Role in Health and Diseases

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“…In addition, apoB is the main ligand for LDL receptor-mediated internalization of LDL particles in tissues. In that context, several polymorphic sites in apoB gene have been studied for their potential links with plasma lipid abnormalities [5,7,19,33] and plasma glucose level [6,13].…”

Section: Introductionmentioning

confidence: 99%

APOB-516 T allele homozygous subjects are unresponsive to dietary changes in a three-month primary intervention study targeted to reduce fat intake

Hammoud¹,

Gastaldi²,

Maillot³

et al. 2009

Genes Nutr

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Dietary guidelines aim to control fat intake and reduce cardiovascular risk but an important interindividual variability occurs among subjects. The objective was to investigate whether the response of lipid and glucose homeostasis parameters after a three-month diet aimed at reducing cardiovascular risk could be modulated by the -516C/T polymorphism in the apolipoprotein B gene (APOB). Middle-aged men (n = 69) and women (n = 100) with moderate cardiovascular disease risk were advised to reduce total energy and fat intakes and replace saturated dietary fat by monounsaturated and polyunsaturated fat. Subjects were genotyped for APOB-516C/T polymorphism. At the entry and at the end of the three-month period, fasting and postprandial plasma lipid analyses were performed. At entry, subjects homozygous for the APOB-516 T allele exhibited significantly lower fasting plasma concentrations of apolipoprotein B 48, triglycerides and triglyceride-rich lipoproteins-triglycerides compared to C carrier subjects. After the diet period, while C carrier subjects presented a clear improvement of most biological parameters, paradoxically T/T subjects did not modify them. In addition, the apoB 48 postprandial response after a standardized mixed test meal was not improved in T/T subjects after the threemonth diet, contrary to C allele carriers. Even though their phenotype at entry does not show any significant increase of risk factors when compared to other groups, subjects homozygous for the APOB-516 T allele are unresponsive to a healthy diet that improves cardiovascular risk status in the whole population.

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Common and Rare Alleles in Apolipoprotein B Contribute to Plasma Levels of Low-Density Lipoprotein Cholesterol in the General Population

Abstract: Multiple common and rare alleles in APOB contribute to plasma levels of LDL cholesterol in the general population, although the effects of common alleles and haplotypes are modest.

Cited by 38 publications

References 23 publications

Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy

Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy

Antioxidant Complexes and Lipoprotein Metabolism – Experience of Grape Extracts Application Under Metabolic Syndrome and Neurogenic Stress

APOB-516 T allele homozygous subjects are unresponsive to dietary changes in a three-month primary intervention study targeted to reduce fat intake

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