Abstract for presentation at 11th International Congress of Human Genetics

USF1 gene variants predispose to dyslipidemias and metabolic syndrome in a 32-year longitudinal follow-up study

  • Kirsi Auro, National Public Health Institute, Dept. of Molecular Medicine, Helsinki, Finland, Finland
  • Kati Komulainen, National Public Health Institute, Dept. of Molecular Medicine, Helsinki, Finland, Finland
  • Björn Zethelius, Dept. of Public Health and Caring Sciences, Uppsala University, Sweden, Sweden
  • Christian Berne, Dept. of Medical Sciences, Uppsala University, Sweden, Sweden
  • Marja-Riitta Taskinen, Dept. of Medicine, Helsinki University Central Hospital, Finland, Finland
  • Leena Peltonen, National Public Health Institute, Dept. of Molecular Medicine, Helsinki, Finland, Finland
  • Markus Perola, National Public Health Institute, Dept. of Molecular Medicine, Helsinki, Finland, Finland
  • Ann-Christine Syvänen, Dept. of Medical Sciences, Uppsala University, Sweden, Sweden

    • Upstream stimulatory factor I (USF1) is a transcription factor, which regulates several genes participating energy, lipid and glucose metabolism. Genetic variants of USF1 have previously been linked to cardiovascular and metabolic traits, and serum lipid levels in several family studies. Our aim was to further address the role of USF1 in metabolic traits studying a large male cohort with 32-year longitudinal follow-up.
    A cohort of all males in Uppsala County, Sweden, born in 1920-1924 (n=2322) was examined at the ages of 50, 60, 70 and 77 years for anthropometric features, blood pressure, and plasma lipid and glucose markers. DNA was drawn at 70 years (n=1157). During the follow-up, altogether 776 individuals developed metabolic syndrome using the ATP III criteria. Within the three haplotype tagging single nucleotide polymorphisms of USF1 genotyped, metabolic syndrome was more common among the minor allele carriers of SNP 1 (p=0.0127) and less common among the minor allele carriers of SNP 2 (p=0.0123). Longitudinal analysis with mixed models revealed that among the metabolic syndrome patients, the carriers of the minor allele of SNP 1 had significantly lower serum triglyceride values than the ones homozygous for the major allele (p=0.008). Serum total cholesterol (p=0.0304) and serum LDL (p=0.0016) concentrations were significantly higher among the SNP 2 major allele carriers, although the minor allele group remained small (n=6). BMI was used as a covariate in all lipid analyses.
    Our results from this unique, 32-year longitudinal follow-up study suggest that genetic variation of USF1 may have a role in the regulation of lipid metabolism, and may influence to metabolic traits at the population level. Importantly, all the lipid trends observed were seen to last throughout the longitudinal follow-up. Further, the concentration of the findings to individuals with metabolic syndrome speaks for underlying gene-gene or gene-environment interaction.

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