Glutamate carboxypeptidase II (GCPII) hydrolyzes polyglutamyl folates before their absorption. Recently, a 1561 C>T polymorphism in the GCPII gene was reported to be associated with lower folate and higher homocysteine plasma concentrations in a small (n = 75) selected elderly population. In this study, we examined the effect of this polymorphism in 680 men and 644 women attending the fifth examination of the Framingham Offspring Study. At the time of sample collection, subjects were not taking any supplements and were not exposed to food folate fortification. GCPII genotypes were determined by allelic discrimination using Taqman probes. In the population as a whole, this mutation was not associated with lower plasma folate level or with elevated plasma homocysteine. In men, plasma folate concentrations were higher in carriers of the T allele compared with those homozygotes of the wild-type allele (P < 0.05), whereas in women folate concentrations did not differ between genotypes (P = 0.8). In its relationship to plasma folate, this mutation exhibited a weak interaction with age and gender only in older women (P = 0.05). Overall, our data show that the GCPII C1561T polymorphism is not a determinant of plasma folate or total homocysteine concentrations in this large cohort of participants from the Framingham Offspring Study.
Polyunsaturated fatty acids (PUFA) contained in fish oil (FO) are ligands for peroxisome proliferator-activated receptors (PPAR) that may induce changes in cardiometabolic markers. Variation in PPAR genes may influence the beneficial responses linked to FO supplementation in young adults. The study aimed to analyze the effect of FO supplementation on glucose metabolism, circulating lipids and inflammation according to PPARα L162V and PPARγ2 P12A genotypes in young Mexican adults. 191 young, non-smoking subjects between 18 and 40 years were included in a one-arm study. Participants were supplemented with 2.7 g/day of EPA+DHA, during six weeks. Dietary analysis, body composition measurements and indicators for glucose metabolism, circulating lipids, and markers for inflammation were analyzed before and after intervention. An overall decrease in triglycerides (TG) and an increase in HS-ω3 index were observed in all subjects [-4.1 mg/dL, (SD:±51.7), P=.02 and 2.6%, (SD:±1.2), P<.001 respectively]. Mean fasting insulin and glycated hemoglobin (HbA1c%) were significantly decreased in all subjects [-0.547mlU/L, (SD:±10.29), P=.034 and-0.07%, (SD:±0.3), P<.001 respectively], whereas there was no change in body composition, fasting glucose, adiponectin and inflammatory markers. Subjects carrying the minor alleles of PPARα L162V and PPARγ2 P12A had higher responses in reduction of TG and fasting insulin respectively. Interestingly, doses below 2.7 g/day (1.8 g/day) were sufficient to induce a significant reduction in fasting insulin and HbA1c% from baseline (P=.019 and P<.001). The observed responses in triglycerides and fasting insulin in the Mexican population give further evidence of the importance of FO supplementation in young people as an early step towards the prevention of cardiometabolic disease.
Description of frequencies and haplotypes in Mexican Mestizo (MM) and Mexican Amerindian (MA) populations, of two SNPs implicated in lipid metabolism, which have been associated to lipid levels in white populations. For this purpose we analyzed DNA extracted from blood samples of 372 MA and 300 MM that participated in the Mexican Genome Diversity Project by allelic discrimination, we also constructed haplotypes and identified tag SNPs.ResultsThe frequency for LIPC rs1800588 was 0.430 in MM and 0.262 in MA, whereas for APOA5 rs662799 the frequency was 0.168 in MM and 0.262 in MA. Three haplotypes (>5%) were identified on the LIPC region on MM, one of them including the rs1800588 (8.3%). Six haplotypes (>5%) were identified on the APOA5 region. The rs662799 SNP was included in haplotypes showing similar frequencies in MM and MA (14% and 14.8% respectively). The APOA5 rs662799 is in high LD with tag SNPs that are present in BUD13 and ZNF259. The LIPC rs1077834, that has been associated to higher high density lipoprotein concentrations in white populations, showed high linkage desequilibrium with our SNP of interest.ConclusionsThe genetic information obtained from this study will be useful in future studies where associations between lipid metabolism phenotypes, environmental factors, and disease onset need to be determine in Mexican population. Source of research support CONACYT.
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