Apolipoprotein E polymorphism in men and women from a Spanish population: allele frequencies and influence on plasma lipids and apolipoproteins

Gómez-Coronado, Diego; Álvarez, Juan José Criado; Entrala, Alfredo; Olmos, José María de Francisco; Herrera, Emílio; Lasunción, Miguel A.

doi:10.1016/s0021-9150(99)00168-9

Cited by 68 publications

(53 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, the effects of the APOE IVS1+69C>G marker on biliary stones and cancer were limited to men, suggesting a gender-specific role of APOE. These findings are noteworthy because previous studies have noted stronger positive associations between the APOE e4 allele and triglyceride levels among men than women (38,39), raising the possibility that the metabolic effect of APOE may contribute to the higher incidence of bile duct and ampullary cancers reported among men than women (1).…”

Section: Discussionmentioning

confidence: 68%

Polymorphisms of Genes in the Lipid Metabolism Pathway and Risk of Biliary Tract Cancers and Stones: A Population-Based Case-Control Study in Shanghai, China

Andreotti

Chen

Gao

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Biliary tract cancers, encompassing the gallbladder, extrahepatic bile duct, and ampulla of Vater, are uncommon yet highly fatal malignancies. Gallstones, the primary risk factor for biliary cancers, are linked with hyperlipidemia. We examined the associations of 12 single nucleotide polymorphisms of five genes in the lipid metabolism pathway with the risks of biliary cancers and stones in a population-based case-control study in Shanghai, China. We included 235 gallbladder, 125 extrahepatic bile duct, and 46 ampulla of Vater cancer cases, 880 biliary stone cases, and 779 population controls. Subjects completed an in-person interview and gave blood. Genotyping was conducted by TaqMan assay using DNA from buffy coats. The effects of APOE IVS1+69 (rs440446) and APOB IVS6+360C>T (rs520354) markers were limited to men. Men carrying the G allele of APOE IVS1+69 had a 1.7-fold risk of stones [95% confidence interval (95% CI), 1.2-2.4], a 1.8-fold risk of gallbladder cancer (95% CI, 1.0-3.3), a 3.7-fold risk of bile duct cancer (95% CI, 2.0-7.0), and a 4-fold risk of ampullary cancer (95% CI, 1.4-12.4). Male carriers of the T allele of APOB IVS6+360C>T had a 2-fold risk of bile duct cancer (95% CI, 1.2-3.4). The APOB T-T haplotype (APOB IVS6+360C>T, EX4+56C>T) was associated with a 1.6-fold risk of bile duct cancer (95% CI, 1.1-2.3). Male and female carriers of the T allele of LDLR IVS9-30C>T (rs1003723) had a 1.5-fold risk of bile duct cancer. Our findings suggest that gene variants in the lipid metabolism pathway contribute to the risk of biliary tract stones and cancers, particularly of the bile duct. (Cancer Epidemiol Biomarkers Prev 2008;17(3):525 -34)

show abstract

Section: Discussionmentioning

confidence: 68%

Polymorphisms of Genes in the Lipid Metabolism Pathway and Risk of Biliary Tract Cancers and Stones: A Population-Based Case-Control Study in Shanghai, China

Andreotti

Chen

Gao

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

show abstract

“…This result is in agreement with that of a Spanish team who found that the influence of apoE on plasma cholesterol was not significant in men. 28 Conflicting results for triglycerides levels are found in the literature. Since triglycerides vary widely among individuals, 3 this variability could mask a clear apoE genotype effect.…”

Section: Discussionmentioning

confidence: 97%

The importance of plasma apolipoprotein E concentration in addition to its common polymorphism on inter-individual variation in lipid levels: results from Apo Europe

et al. 2002

View full text Add to dashboard Cite

Interindividual variation in the concentration of plasma lipids which are associated with coronary artery disease (CAD) risk is determined by a combination of genetic and environmental factors. This study investigates the effects of apoE genotype and plasma concentration on cholesterol and triglycerides (TG) levels in subjects from five countries: Finland, France, Northern Ireland, Portugal, and Spain. Age and sex significantly influenced serum cholesterol, TG and apoE concentrations. The age effect differs in males and females. The allele frequencies of the apoE gene, one of the most widely studied CAD susceptibility genes, were determined: the e2 allele frequency and the apoE concentration showed a north -south increasing gradient while the e4 allele frequency showed the reverse. ApoE plays an important role in lipid metabolism. Total cholesterol and TG concentrations were significantly dependent on apoE genotype in both sexes. These differences in lipids between genotypes were more pronounced when plasma apoE concentrations were taken into account.

show abstract

“…It is accepted that variations in plasma lipid levels are determined, in part, by polymorphisms in the apo E gene (7)(8)(9)(10)(11)(12)(13) and also by birth or infancy weight (19). However, the interaction of anthropometric variables with the specific effects of apo E genotype on those variables remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have documented the impact of these mutations on CHD (4 -6) and the effects of these alleles on the normal variation of lipid levels in adult populations. Heterozygous subjects for the ⑀2 and ⑀4 alleles had, respectively, lower and higher total cholesterol (TC) and LDL-C levels than subjects carrying the ⑀3⑀3 genotype (7)(8)(9). This influence of the apo E polymorphisms on the metabolism of the apo B-containing lipoproteins appears to be present in the 1st years of life (10 -13).…”

mentioning

confidence: 99%

Influence of Birth Weight on the Apo E Genetic Determinants of Plasma Lipid Levels in Children

et al. 2002

View full text Add to dashboard Cite

To evaluate the influence of birth weight on apolipoprotein (apo) E genetic determinants of plasma lipids levels in prepubertal children we studied 933 healthy children (491 males and 442 females) 6 to 8 years old (mean age of 6.7 y), whose weight was recorded at birth. Plasma lipid and apolipoprotein concentrations and apo E genotypes were determined. We observed a greater effect of the apo E polymorphism on total cholesterol (TC), LDL-cholesterol (LDL-C) and especially apo B levels in children with birth weight in the lower tertile compared with those with birth weights in higher tertiles. Taking the ⑀3 allele homozygosity as reference, in boys with birth weights in the low tertile the overall lowering effect of the ⑀2 allele on TC, LDL-C and apo B was greater (10.5% (p Ͻ 0.01), 20.2% (p Ͻ 0.01) and 18.8% (p Ͻ 0.01), respectively) than in those in the highest tertile (5.6% on TC, 10.3% on LDL-C and 12.6% (p Ͻ 0.01) on apo B). A similar trend in this effect between tertiles of birth weight was also observed in girls. For both sexes, linear regression analysis demonstrates a positive and significant interaction between birth weight and ⑀2, which may explain the fact that the decrease in TC, LDL-C and apo B associated with the ⑀2 allele is more marked the lower the birth weight. Taking into account the prevalence of apo E polymorphism, and that appears to be the main genetic factor affecting plasma lipids, the interaction of apo E genotype and birth weight could be an important determinant of TC, LDL-C and apo B levels, and, as a consequence, of atherosclerosis. (Pediatr Res 52: 873-878, 2002) Abbreviations apo, apolipoprotein TC, total cholesterol TG, triglycerides HDL-C, HDL-cholesterol LDL-C, LDL-cholesterol CHD, coronary heart disease Coronary heart disease (CHD) and its risk factors, including abnormalities in lipid metabolism, are associated with small size at birth and low weight during infancy (1, 2). Genetic composition also determines differences in plasma lipid levels and susceptibility to atherosclerosis. Although the risk of CHD due to both environmental and genetic influences is well known, the extent of interactions between these factors has not been well characterized.Apolipoprotein E (apo E) is one of the key regulators of plasma lipid levels by affecting the hepatic binding, uptake, and catabolism of several classes of lipoproteins (3). Apo E genotypes are one of the most important genetic determinants of atherogenesis. Apo E appears in three isoforms E2, E3, and E4, encoded by the corresponding alleles ⑀2, ⑀3, and ⑀4. Previous studies have documented the impact of these mutations on CHD (4 -6) and the effects of these alleles on the normal variation of lipid levels in adult populations. Heterozygous subjects for the ⑀2 and ⑀4 alleles had, respectively, lower and higher total cholesterol (TC) and LDL-C levels than subjects carrying the ⑀3⑀3 genotype (7-9). This influence of the apo E polymorphisms on the metabolism of the apo B-containing lipoproteins appears to be present in the 1st years of li...

show abstract

Apolipoprotein E polymorphism in men and women from a Spanish population: allele frequencies and influence on plasma lipids and apolipoproteins

Cited by 68 publications

References 42 publications

Polymorphisms of Genes in the Lipid Metabolism Pathway and Risk of Biliary Tract Cancers and Stones: A Population-Based Case-Control Study in Shanghai, China

Polymorphisms of Genes in the Lipid Metabolism Pathway and Risk of Biliary Tract Cancers and Stones: A Population-Based Case-Control Study in Shanghai, China

The importance of plasma apolipoprotein E concentration in addition to its common polymorphism on inter-individual variation in lipid levels: results from Apo Europe

Influence of Birth Weight on the Apo E Genetic Determinants of Plasma Lipid Levels in Children

Contact Info

Product

Resources

About