Integrative Genetic Analysis of DPP4-Related Variants Reveals Risk Patterns for Type 2 Diabetes and Cardiometabolic...

Area of Science:

• Genetics
• Endocrinology
• Cardiovascular Medicine

Background:

• Type 2 diabetes mellitus (T2DM) frequently co-occurs with hypertension (HTN) and dyslipidemia (DYS), elevating cardiovascular risk.
• The genetic basis for this clustering of conditions within the DPP4-ABCC8-INSR-IGF1 axis is under investigation.

Purpose of the Study:

• To investigate the association between genetic variations in the DPP4-ABCC8-INSR-IGF1 axis and the co-occurrence of HTN and DYS in T2DM patients.
• To identify specific genetic markers and haplotypes linked to the susceptibility of developing HTN and DYS in the context of T2DM.

Main Methods:

• Stratified 444 T2DM patients into T2DM, T2DM with HTN (T2MH), and T2DM with HTN and DYS (T2MH-DYS) groups.
• Genotyped six single nucleotide polymorphisms (SNPs) and performed logistic regression and haplotype analyses with Bonferroni correction.

Main Results:

• DPP4 rs3788979 variants (CT/CC) showed a protective effect against HTN but increased DYS risk when co-occurring with HTN.
• IGF1 rs972936 TC genotype was associated with reduced T2MH risk.
• Haplotype analysis identified GAATGT as protective against HTN and GACCGT as a risk haplotype for DYS, both remaining significant after correction.

Conclusions:

• Genetic variations within the DPP4 axis significantly influence susceptibility to HTN and DYS in T2DM.
• The DPP4 rs3788979 genotype's risk profile is modulated by lipid status, highlighting gene-environment interactions.
• GAATGT and GACCGT are robust haplotype markers for HTN and DYS, respectively, in T2DM patients.