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. 2021 Jun 11:12:592646.
doi: 10.3389/fgene.2021.592646. eCollection 2021.

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

Gilberto Vargas-Alarcón  1 , María Del Carmen González-Salazar  2 , Christian Vázquez-Vázquez  1 , Adrián Hernández-Díaz Couder  3 , Fausto Sánchez-Muñoz  3 , Juan Reyes-Barrera  2 , Sergio A Criales-Vera  4 , Marco Sánchez-Guerra  5 , Citlalli Osorio-Yáñez  6 , Rosalinda Posadas-Sánchez  2
Affiliations

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

Gilberto Vargas-Alarcón et al. Front Genet. .

Abstract

Dipeptidyl peptidase-4 (DPP4) can influence lipid homeostasis and atherosclerosis progression. We aimed to assess the association of DPP4 gene polymorphisms with hypoalphalipoproteinemia and DPP4 serum levels, in a cohort of Mexican individuals. Five DPP4 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 (OR = 0.22, P heterozygote = 0.001) and rs17574 (OR = 0.78, P additive = 0.022; OR = 0.73, P dominant = 0.012; OR = 0.73, P heterozygote = 0.017; OR = 0.72, P codominant 1 = 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 DPP4 minor alleles were associated with protection for the presence of insulin resistance (IR) (OR = 0.17, P heterozygote = 0.019 for rs12617336 and OR = 0.75, P additive = 0.049 for rs17574). The rs12617336 minor allele was also associated with a low risk of hyperinsulinemia (OR = 0.11, P heterozygote = 0.006). Differences in DPP4 levels were observed in individuals with rs17574 genotypes, the rs17574 GG genotype individuals had the lowest levels. Our data suggest that rs12617336 and rs17574 DPP4 minor alleles could be envisaged as protective genetic markers for hypoalphalipoproteinemia, IR, and hyperinsulinemia. The rs17574 GG genotype was associated with the lowest DPP4 levels.

Keywords: DPP4 serum levels; Dipeptidyl peptidase-4; hyperinsulinemia; hypoalphalipoproteinemia; insulin resistance; polymorphism.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Association of DPP4 polymorphisms with hypoalphalipoproteinemia. MAF, minor allele frequency. All models were adjusted by age, sex, BMI, current smoking, physical activity, visceral abdominal fat, and triglycerides levels. The reference genotype was GG for rs12617336 and AA for rs17574. HA: hypoalphalipoproteinemia; Non-HA: non-hypoalphalipoproteinemia.
FIGURE 2
FIGURE 2
DPP4 concentration in the whole sample stratified by (A) in non-hypoalphalipoproteinemia and hypoalphalipoproteinemia groups; (B) in rs17574 genotypes; (C) in non-carries (AA) and carriers (AG + GG) of rs17574 minor allele. HA: Hypoalphalipoproteinemia; Non-HA: non-hypoalphalipoproteinemia.
FIGURE 3
FIGURE 3
DPP4 concentration in non-hypoalphalipoproteinemia (A,B) and hypoalphalipoproteinemia (C,D) groups, stratified by rs17574 genotypes (A,C) and in non-carries (AA) and carriers (AG + GG) of rs17574 minor allele (B,D).
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