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.