Longitudinal Changes in Triglycerides According to ANGPTL4[E40K] Genotype and Longitudinal Body Weight Change in the Atherosclerosis Risk in Communities Study

Purpose: Allelic variation in the adipokine angiopoietin-like 4 gene (ANGPTL4[E40 K]) has been cross-sectionally associated with triglycerides, but the effects of genotype, or the interaction between genotype and body weight, on longitudinal triglyceride change have not been studied. Methods: Body weight, triglycerides, and ANGPTL4[E40 K] genotype were determined at baseline (1987-1989) and at 3 follow-up exams (1990-1992, 1993-1995, 1996-1998) in 7,939 white ANGPTL4[E40 K] G allele homozygotes and 344 A allele carriers. Changes in body weight and triglycerides were characterized as the difference between exam 4 and baseline measurements. Results: ANGPTL4[E40 K] A allele carriers had triglyceride concentrations that were 15 to 18 mg/dL lower than G allele homozygotes at all exams (P < 0.0001). Triglycerides increased in both genotype groups over the 9-year period (+19.1 ± 0.9 and +16.2 ± 4.1 mg/dL in GG and GA/AA, respectively; P difference, 0.48). Weight gain was associated with increased triglycerides to a comparable degree in both genotype groups (+5.5 ± 0.3 and +4.3 ± 0.9 mg/dL per 2-kg increase in body weight in GG and GA/AA, respectively, p interaction = 0.30). Conclusions: Differences in triglyceride concentrations between ANGPTL4[E40 K] A allele carriers and G allele homozygotes are maintained over time, but the degree of increase in triglycerides was similar between groups and was not modified by body weight changes.