• Association of apolipoprotein E gene polymorphisms with blood lipids and their interaction with dietary factors

      Shatwan, Israa M.; Winther, Kristian H.; Ellahi, Basma; Elwood, Peter; Ben-Shlomo, Yoav; Givens, Ian; Rayman, Margaret P.; Lovegrove, Julie A.; Vimaleswaran, Karani S.; Hugh Sinclair Unit of Human Nutrition and Institute for Cardiovascular and Metabolic Research (ICMR), Department of Food and Nutritional Sciences, University of Reading, Reading, UK, RG6 6AP, UK; Food and Nutrition Department, Faculty of Home Economics, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Endocrinology and Metabolism Odense University Hospital Denmark; Faculty of Health and Social Care, University of Chester, Chester, CH1 1SL, UK; Department of Epidemiology, Statistics and Public Health, Cardiff University, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK; Population Health Sciences, University of Bristol, Bristol, BS8 2PS, UK; Institute for Food, Nutrition and Health, University of Reading, Earley Gate, Reading RG6 6AR, UK; Department of Nutritional Sciences Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK. (BMC, 2018-04-30)
      Abstract Background: Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors. Methods: The population studied for this investigation included 660 individuals from the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1,238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ) in PRECISE and a validated semi-quantitative FFQ in the CaPS. Interaction analyses were performed by including the interaction term in the linear regression model adjusted for age, body mass index, sex and country. Results: There was no association between dietary factors and blood lipids after Bonferroni correction and adjustment for confounding factors in either cohort. In the PRECISE study, after correction for multiple testing, there was a statistically significant association of the APOE haplotype (rs7412 and rs429358; E2, E3, and E4) and APOE tagSNP rs445925 with total cholesterol (P=4x10-4 and P=0.003, respectively). Carriers of the E2 allele had lower total cholesterol concentration (5.54± 0.97 mmol/L) than those with the E3 (5.98± 1.05 mmol/L) (P=0.001) and E4 (6.09± 1.06 mmol/L) (P=2x10-4) alleles. The association of APOE haplotype (E2, E3, and E4) and APOE SNP rs445925 with total cholesterol (P=2x10-6 and P=3x10-4, respectively) was further replicated in the CaPS. Additionally, significant association was found between APOE haplotype and APOE SNP rs445925 with low density lipoprotein cholesterol in CaPS (P=4x10-4 and P=0.001, respectively). After Bonferroni correction, none of the cohorts showed a statistically significant SNP-diet interaction with lipid outcomes. Conclusion: In summary, our findings from the two cohorts confirm that genetic variations at the APOE locus influence plasma total cholesterol concentrations, however, the gene-diet interactions on lipids require further investigation in larger cohorts.