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Effect of the SORT1 low-density lipoprotein cholesterol locus is sex-specific in a fit, Canadian young-adult population.

The SORT1 locus was originally identified by genome-wide association studies of low-density lipoprotein cholesterol (LDL-C) in adults. Although the effect sizes of this locus are relatively small, we hypothesized that a younger population would show a greater genetic effect because of fewer confounding variables. As such, we investigated the association between the SORT1 locus and LDL-C in a group of healthy young adults. Subjects (n = 122, mean age = 23.2 years) were recruited from the University of Calgary. Lipid measures and genomic DNA were collected from peripheral blood after an overnight fast. Blood pressure, percent body fat (%BF), and maximal oxygen consumption were also measured. Associations between genotype and LDL-C were investigated using linear regression. Nearly one half (42.9%) of the female and 21.7% of the male subjects had a %BF that was above a healthy range. More than one quarter of the subjects had LDL-C values that were considered nonoptimal. Although the association was not significant when both sexes were combined, a significant association was observed between the SORT1 locus (GG: 2.46 ± 0.11 mmol·L(-1) vs. GT-TT: 2.06 ± 0.12 mmol·L(-1), p = 0.016) and LDL-C in male subjects, with genotype explaining 3.0% of the variability in LDL-C. A high prevalence of nonoptimal LDL-C exists in this young population even though it is otherwise fit and healthy. A significant association was found between LDL-C and the minor SORT1 allele in male subjects, with an effect size larger than previously reported in older populations. SORT1 is a valuable target for identifying individuals who would most benefit from early interventions to prevent cardiovascular disease.