AUTHOR=Vargas-Alarcón Gilberto , González-Salazar María del Carmen , Vázquez-Vázquez Christian , Hernández-Díaz Couder Adrián , Sánchez-Muñoz Fausto , Reyes-Barrera Juan , Criales-Vera Sergio A. , Sánchez-Guerra Marco , Osorio-Yáñez Citlalli , Posadas-Sánchez Rosalinda 

TITLE=The rs12617336 and rs17574 Dipeptidyl Peptidase-4 Polymorphisms Are Associated With Hypoalphalipoproteinemia and Dipeptidyl Peptidase-4 Serum Levels: A Case-Control Study of the Genetics of Atherosclerotic Disease (GEA) Cohort

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.592646

DOI=10.3389/fgene.2021.592646

ISSN=1664-8021

ABSTRACT=<p>Dipeptidyl peptidase-4 (DPP4) can influence lipid homeostasis and atherosclerosis progression. We aimed to assess the association of <italic>DPP4</italic> gene polymorphisms with hypoalphalipoproteinemia and DPP4 serum levels, in a cohort of Mexican individuals. Five <italic>DPP4</italic> polymorphisms (rs12617336, rs12617656, rs1558957, and rs3788979, and rs17574) were genotyped in 748 participants with and 745 without hypoalphalipoproteinemia. The associations were evaluated using logistic regression analyses. Under inheritance models adjusted for confounding variables, the rs12617336 (<italic>OR</italic> = 0.22, <italic>P</italic><sub>heterozygote</sub> = 0.001) and rs17574 (<italic>OR</italic> = 0.78, <italic>P</italic><sub>additive</sub> = 0.022; <italic>OR</italic> = 0.73, <italic>P</italic><sub>dominant</sub> = 0.012; <italic>OR</italic> = 0.73, <italic>P</italic><sub>heterozygote</sub> = 0.017; <italic>OR</italic> = 0.72, <italic>P</italic><sub>codominant</sub><sub>1</sub> = 0.014) minor alleles were associated with a low risk of hypoalphalipoproteinemia. After the correction for multiple comparisons, the associations were marginal except the association of the rs12617336 that remaining significant. Additionally, both <italic>DPP4</italic> minor alleles were associated with protection for the presence of insulin resistance (IR) (<italic>OR</italic> = 0.17, <italic>P</italic><sub>heterozygote</sub> = 0.019 for rs12617336 and <italic>OR</italic> = 0.75, <italic>P</italic><sub>additive</sub> = 0.049 for rs17574). The rs12617336 minor allele was also associated with a low risk of hyperinsulinemia (<italic>OR</italic> = 0.11, <italic>P</italic><sub>heterozygote</sub> = 0.006). Differences in DPP4 levels were observed in individuals with rs17574 genotypes, the rs17574 <italic>GG</italic> genotype individuals had the lowest levels. Our data suggest that rs12617336 and rs17574 <italic>DPP4</italic> minor alleles could be envisaged as protective genetic markers for hypoalphalipoproteinemia, IR, and hyperinsulinemia. The rs17574 <italic>GG</italic> genotype was associated with the lowest DPP4 levels.</p>