Study of the association of SNP in GALNT2, TRIB1 and CELSR2 with plasma lipids in a high cardiovascular risk Spanish population and its modulation by the mediterranean diet

Abstract

Introduction: Genome-wide association (GWA) studies have identified new genetic determinants of plasma lipids. Among them CELSR2/SORT1 (Cadherin, EGF LAG seven-pass G-type receptor 2/ Sortilin 1), TRIB1 (Tribbles homolog 1) and GALNT2 (UDP-Nacetyl-alpha-D-galactosamine: polype ptide N-acetylgalactosaminyltransferase 2), were associated with LDL-C, triglyceridesand HDL-C/ triglycerides, respectively. However, further replication has been modest and none of these studies evaluated the potential modulation by the Mediterranean diet (MEDiet). Methods: We analyzed the association between rs4846914 in GALNT2, rs17321515 in TRIB1 and rs646776 near CELSR2/SORT1 and plasma lipids as well as their modulations by adherence to the MEDiet in a high cardiovascular risk population (1011 participants in the PREDIMED-Valencia study, aged 67+/-7 years), that fulfilled at least one of two criteria: type 2 diabetes; 3 or more cardiovascular risk factors. Subjects with triglycerides >600 mg/dL were excluded. Adherence to MEDiet was assessed by a 14-item questionnaire. Values of 0 or 1 were assigned, and the greater score, the greater the adherence. Two groups were considered (high and low). Results: Prevalence of rs4846914 was 45% AA, 43% AG and 12% GG; rs17321515 was 31% AA, 50% AG and 19% GG; and rs646776 were 65% CC, 32% CG and 3% GG. The TRIB1 rs646776 variant allele was associated with lower triglycerides (137, 126 and 124 mg/dL for AA, AG and GG, respectively; P=0.038) in the whole population. Although a trend to lower LDL-C in CC subjects for the rs646776 as well as a trend to higher trigyclerides in G allele carriers of the rs4846914 was observed, we did not detect statistically significant differences for any SNP. Adherence to the MEDiet modulated some of these associations. Thus, a low MEDiet score increased LDL-C concentrations in CC subjects (rs646776), resulting in significant differences between genotypes (P=0.035). Conclusions: The rs17321515 in TRIB1 was associated with triglyceride concentrations, whereas rs4846914 and rs646776 were modulated by the MEDiet.