The APOB insertion/deletion polymorphism (rs17240441) influences postprandial lipaemia in healthy adults

Abstract

Background: Apolipoprotein (apo)B is the structural apoprotein of intestinally- and liver- derived lipoproteins and plays an important role in the transport of triacylglycerol (TAG) and cholesterol. Previous studies have examined the association between the APOB insertion/deletion (ins/del) polymorphism (rs17240441) and postprandial lipaemia in response to a single meal; however the findings have been inconsistent with studies often underpowered to detect genotype-lipaemia associations, focused mainly on men, or with limited postprandial characterisation of participants. In the present study, using a novel sequential test meal protocol which more closely mimics habitual eating patterns, we investigated the impact of APOB ins/del polymorphism on postprandial TAG, non-esterified fatty acids, glucose and insulin levels in healthy adults.

Findings: Healthy participants (n = 147) consumed a standard test breakfast (0 min; 49 g fat) and lunch (330 min; 29 g fat), with blood samples collected before (fasting) and on 11 subsequent occasions until 480 min after the test breakfast. The ins/ins homozygotes had higher fasting total cholesterol, LDL-cholesterol, TAG, insulin and HOMA-IR and lower HDL-cholesterol than del/del homozygotes (P < 0.017). A higher area under the time response curve (AUC) was evident for the postprandial TAG (P < 0.001) and insulin (P = 0.032) responses in the ins/ins homozygotes relative to the del/del homozygotes, where the genotype explained 35% and 7% of the variation in the TAG and insulin AUCs, respectively.

Conclusions: In summary, our findings indicate that the APOB ins/del polymorphism is likely to be an important genetic determinant of the large inter-individual variability in the postprandial TAG and insulin responses to dietary fat intake.

Keywords: APOB gene; Insertion/deletion polymorphism; Postprandial study; Sequential test meals; Signal peptide polymorphism; Triacylglycerol.

Figure 1

Effect of APOB ins/del polymorphism on postprandial triacylglycerol (TAG) and insulin response. A. Mean (SEM) for the postprandial TAG response in the APOB del/del (n = 52, open circles), del/ins (n = 70, open squares) and ins/ins (n = 25, open triangles) genotype groups after consumption of a test breakfast (49 g fat) at 0 min and a test lunch (29 g fat) at 330 min. There was a 44% and 31% higher TAG area under the curve (AUC) (del/del vs ins/del, P = 0.010; del/del vs ins/ins, P < 0.001; ins/del vs ins/ins, P < 0.001) in the ins/ins than del/del homozygotes and ins/del heterozygotes, respectively. B. Mean (SEM) for the AUC for the postprandial TAG response in men and women in the APOB del/del (white bars; n = 36 men/n = 16 women), del/ins (black bars; n = 51 men/n = 17 women) and ins/ins (dotted bars; n = 23 men/n = 2 women) genotype groups. There was a significant effect of genotype on the TAG AUC in men only (P = 0.043, del/del vs ins/del; P < 0.001, ins/ins vs both del/del and ins/del) whereas differences between genotypes were not evident in women (P > 0.501). C. Mean (SEM) for the postprandial insulin response in the APOB del/del (n = 10, open circles), del/ins (n = 15, open squares) and ins/ins (n = 10, open triangles) genotype groups after consumption of a test breakfast (49 g fat) at 0 min and a test lunch (29 g fat) at 330 min. There was a 69% higher AUC in the ins/ins than ins/del (P = 0.004) and del/del (P = 0.032) groups.