Studies of association between LPIN1 variants and common metabolic phenotypes among 17 538 Danes

Objective: Lipin-1, encoded by LPIN1, is expressed in the major metabolically active tissues. Decreased expression of lipin-1 in adipose tissue correlates with increased insulin resistance, and tagging of the LPIN1 locus has shown that rs33997857, rs6744682, and rs6708316 associate with metabolic phenotypes, specifically body mass index (BMI) and fasting serum lipid levels, both on the individual single-nucleotide polymorphism level and with a three-marker haplotype. Our aim was to validate the reported findings in the Danish population. Design: In the present study, variants were analyzed in LPIN1 using case-control studies, haplotype analyses, and quantitative trait analyses in a population of 17 538 Danes. Methods: The three LPIN1 variants were genotyped in 17 538 Danes from four study populations of middle-aged people. This provided us with a statistical power >99% to replicate previous findings. Variants were analyzed individually and in haplotype combinations in studies of quantitative metabolic traits and in case-control studies. Results: None of the three variants were associated with the examined quantitative traits including BMI, waist circumference, blood pressure, fasting serum lipid concentrations, or plasma glucose or serum insulin concentrations in the fasting state and following an oral glucose tolerance test. Haplotypes were tested for association with quantitative traits; however, only nominal association with blood pressure (P=0.04) and waist circumference (P=0.04) was observed. In case-control studies, no association was found for individual variants or the three-marker haplotype. Conclusion: LPIN1 rs33997857, rs6744682, and rs6708316 did not associate with type 2 diabetes, obesity, or related quantitative metabolic phenotypes in the Danish population examined.