Functional Variants of Lipid Level Modifier MLXIPL, GCKR, GALNT2, CILP2, ANGPTL3 and TRIB1 Genes in Healthy Roma and Hungarian Populations

Abstract

The role of triglyceride metabolism in different diseases, such as cardiovascular or cerebrovascular diseases is still under extensive investigations. In genome-wide studies several polymorphisms have been reported, which are highly associated with plasma lipid level changes. Our goal was to examine eight variants: rs12130333 at the ANGPTL3, rs16996148 at the CILP2, rs17321515 at the TRIB1, rs17145738 and rs3812316 of the MLXIPL, rs4846914 at GALNT2, rs1260326 and rs780094 residing at the GCKR loci. A total of 399 Roma (Gypsy) and 404 Hungarian population samples were genotyped using PCR-RFLP method. Significant differences were found between Roma and Hungarian population samples in both MLXIPL variants (C allele frequency of rs17145738: 94.1% vs. 85.6%, C allele frequency of rs3812316: 94.2% vs. 86.8% in Romas vs. in Hungarians, p < 0.05), in ANGPTL3 (T allele frequency of rs1213033: 12.2% vs. 18.5% in Romas vs. Hungarians, p < 0.05) and GALNT2 (G allele frequency of rs4846914: 46.6% vs. 54.5% Romas vs. in Hungarians, p < 0.05), while no differences over SNPs could be verified and the known minor alleles showed no correlation with triglyceride levels in any population samples. The current study revealed fundamental differences of known triglyceride modifying SNPs in Roma population. Failure of finding evidence for affected triglyceride metabolism shows that these susceptibility genes are much less effective compared for example to the apolipoprotein A5 gene.

TRIB1 rs17321515 gene polymorphism increases the risk of coronary heart disease in general population and non-alcoholic fatty liver disease patients in Chinese Han population

“…Moreover, TRIB1 rs17321515 A allele could affect the serum lipids levels such as FPG, HDL, and TC in each group. Our conclusion is consistent with the previous studies which were conducted in other countries [26, 43, 45].…”

“…In a Chinese Han cohort study, TRIB1 rs17321515 AA genotype carriers had higher TG level than GG genotype carriers [42]. Katalin et al also found that TRIB1 rs17321515 AA genotype carriers had higher serum TG and TC levels than GG + GA genotypes carriers [43]. In consideration of the higher mortality rate of NAFLD-related CHD than the single liver disease, it is meaningful to investigate the effect of TRIB1 rs17321515 gene polymorphism on the risk of CHD in general population and NAFLD patients, and the effect on the serum lipids levels [4, 44].…”

New insights into ANGPLT3 in controlling lipoprotein metabolism and risk of cardiovascular diseases

“…Besides these three SNPs loci, rs12130333 was closely associated with the Fredrickson hyperlipoproteinemia type 5, characterized by a mixed hyperlipidaemia of elevated levels of VLDL and CM [ 36 ]. On the contrary, rs2131925 was shown to be associated with a mean reduction in plasma TG of 4.94 mg/dl [ 37 ], and the patients carried rs12042319 was also presented lower LDL-C and TG levels [ 38 ]. Another exon sequencing result of the 7 exons of a multi-ethnic sample of 3551 individuals in the Dallas Heart Study provided evidence for a link between the ANGPTL3 gene variant and plasma TG levels.…”

Distinct Penetrance of Obesity-Associated Susceptibility Alleles in the Hungarian General and Roma Populations

“…Despite the fact that today's Hungarian Gypsies have genetic variants typical of India and Europe, the two populations fundamentally differ from each other in their genetic architectures [4,5]. Recent genetic epidemiological studies also indicated significant genetic differences between the Hungarian general (HG) and Hungarian Roma (HR) populations [6,7,8,9]. …”