The association of common genetic variants in the APOA5, LPL and GCK genes with longitudinal changes in metabolic and cardiovascular traits

Abstract

Aims/hypothesis Common genetic variants influence plasma triacylglycerol, HDL-cholesterol (HDL-C) and glucose levels in cross-sectional studies. However, the longitudinal effects of these established variants have not been studied. Our aim was to examine the longitudinal associations of four such variants in the apolipoprotein A-V (APOA5), lipoprotein lipase (LPL), and glucokinase (GCK) genes with fasting glucose or lipid levels. Methods The individuals analysed were participants in the Busselton Health Survey (n=4,554). Cross-sectional analyses of family data used the total association test. Longitudinal association analyses of unrelated participant data (n=2,864) used linear mixed-effects models. Results The findings of cross-sectional association analyses replicated those of previous studies. We observed associations of the G and C alleles at the APOA5 single nucleotide polymorphisms (SNPs) rs662799 and rs3135506 with raised triacylglycerol levels (p=0.0003 and p<0.0001, respectively), the 447X allele at the LPL SNP rs328 with reduced triacylglycerol levels (p=0.0004) and raised HDL-C levels (p=0.0004), and the A allele of the GCK SNP rs1799884 with raised fasting glucose level (p=0.015). Longitudinal association analyses showed that most of these associations did not change in the same individuals over an average follow-up time of 17.4 years, though there was some evidence that the association of the 447X allele of rs328 with raised HDL-C level significantly increased with age (p=0.01), and that the association of the C allele of rs3135506 with raised triacylglycerol level significantly increased over time (p=0.0007).Conclusions/interpretation The current study suggests that the effects of established gene variants on lipid and glucose traits do not tend to alter with age during adulthood or over time.

A Lipoprotein Lipase Gene Polymorphism Interacts with Consumption of Alcohol and Unsaturated Fat to Modulate Serum HDL-Cholesterol Concentrations

“…Although evidence is still limited, LPL activity seems to be modified by aging (32) and lifestyle (33) as well as by carrying particular polymorphisms in the LPL gene (34). Recent studies have reported some common polymorphisms that are significantly associated with longitudinal variations in HDL-C concentrations (35,36). In a 20-y follow-up study, Tang et al (35) observed that several common polymorphisms, including rs328 (S4473), rs326, and rs13702, in LPL are significantly 1 Log-transformed serum concentrations measured after 6 y were used.…”

An interaction effect between glucokinase gene variation and carbohydrate intakes modulates the plasma triglyceride response to a fish oil supplementation

“…For C/C homozygotes, low CHO intakes were associated with an increase in plasma TG concentrations, whereas when CHO intakes were high, they had the greatest decrease in their plasma TG concentrations following the fish oil supplementation of all genotype groups. The SNP rs741038 is an intronic SNP with no potential regulatory impact and is not in LD with rs1799884 or rs2070971 which have been associated previously with plasma TG levels, fasting glucose and/or type 2 diabetes risk (Asselbergs et al 2012;Holmkvist et al 2008;Sotos-Prieto et al 2013;Webster et al 2009;Hu et al 2010;Wang et al 2013). However, it is possible that rs741038 is in LD with other unknown functional SNPs.…”

Gene polymorphisms and gene scores linked to low serum carotenoid status and their associations with metabolic disturbance and depressive symptoms in African-American adults

“…For lipoprotein lipase ( LPL ) related SNPlcar 23 (rs328:G/C; GG vs. CC, mainly low α -carotene (22; 30) ), two previous studies conducted among Caucasian adults also indicated that the “C” allele was consistently linked to HDL-C dyslipidemia, (63; 65) with one of them observing an additional link to TG-dyslipidemia. (65) However, a recent meta-analysis showed only a modest relationship between rs328:G/C and both types of dyslipidemia.…”

“…(65) However, a recent meta-analysis showed only a modest relationship between rs328:G/C and both types of dyslipidemia. (66) Prior to correction for multiple testing, our study was indicative of a consistent relationship in which the “G” allele was associated with a lower odds of elevated HOMA-IR (OR=0.66; 95%CI:0.44–0.98; p=0.037), ( OSM 5 ).…”