Abstract for presentation at 11th International Congress of Human Genetics

The LPIN1 gene is associated with obesity and cardiovascular risk factors at the population level

  • Kati Komulainen, National Public Health Institute, Dept. of Molecular Medicine, Finland
  • Kaisa Silander, National Public Health Institute, Dept. of Molecular Medicine, Finland
  • Elina Suviolahti, National Public Health Institute, Dept. of Molecular Medicine, Finland
  • Veikko Salomaa, National Public Health Institute, Dept. of Epidemiology and Health Promotion, Finland
  • Markus Perola, National Public Health Institute, Dept. of Molecular Medicine, Finland
  • Leena Peltonen, National Public Health Institute, Dept. of Molecular Medicine, Finland

    • Data from mouse studies indicate that lipin, the novel molecular protein expressed by adipocytes, has marked effects on adipose tissue mass. In the mouse, lipin deficiency results in lipodystrophy and insulin resistance, whereas excess lipin levels promote fat accumulation and insulin sensitivity (Peterfy et al. 2001, Phan and Reue 2005). Our recent data revealed negative correlation between lipin transcript levels in adipose tissue and glucose levels, insulin levels, and HOMA-IR (Suviolahti et al. 2006). Further, SNP-defined allelic haplotypes of LPIN1 revealed association with serum insulin levels and BMI in dyslipidemic families and obese individuals (Suviolahti et al.2006). Both the expression levels in adipose tissue across species and genetic data in human study samples would thus imply the importance of lipin in glucose homeostasis and suggest the importance of LPIN1 gene for human metabolic traits.
    Here we studied the allelic variants of the LPIN1 gene in a prospective case-cohort design, FINRISK 92, to assess the significance of the gene as a risk factor for obesity, variation in serum lipid levels and cardiovascular disease (CVD) at the population level. In a subcohort (N=324) representative of the non-cardiovascular individuals of the original follow-up cohort of 5999 Finns, we observed an association between LPIN1 and BMI, HDL-C and total cholesterol to HDL-C ratio (P=0.01-0.05). When the incident CVD cases (N=256) of the follow-up period were examined, we observed variation at the LPIN1 locus to associate with BMI, waist-to-hip ratio, HDL-C, total cholesterol to HDL-C ratio, total cholesterol and triglycerides (P=0.002-0.05). Further, results from Cox proportional hazards analysis suggested that allelic variation of LPIN1 contributes to the risk of CVD (P=0.0005-0.05).These results underline the importance of the LPIN1 gene variants as an obesity and CVD risk factor also at the population level.

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