Low C-Reactive Protein Alleles in Hepatocyte Nuclear Factor 1A Are Associated With an Increased Risk of Cardiovascular Disease

Abstract

Abstract Context Rare variants in HNF1A cause both maturity onset diabetes of the young 3 (HNF1A-MODY) and reduced serum C-reactive protein (CRP) levels. Common variants of HNF1A are associated with serum CRP and type 2 diabetes mellitus (T2DM), but inconsistently with cardiovascular disease (CVD). Objective Our study aimed to investigate the association of low CRP alleles in HNF1A with CVD and indirectly evaluate the CVD risk of HNF1A-MODY patients because of unavailability of enough cases to study their clinical outcomes. Methods A literature search was performed using PubMed, Embase, and Cochrane Library databases from inception to December 2023. All relevant studies concerning the association of HNF1A with CRP, CVD, lipids, and T2DM were included. Odds ratios (ORs), 95% CIs, and study characteristics were extracted. Results Three common coding variants of HNF1A (rs1169288, rs2464196, and rs1169289) were examined. The minor alleles of these variants correlated with low CRP levels (OR 0.89; 95% CI, 0.86-0.91; OR 0.89; 95% CI, 0.88-0.91; OR 0.89; 95% CI, 0.88-0.91, respectively). Their low CRP alleles were associated with increased risk of CVD (OR 1.03; 95% CI, 1.03-1.04), higher low-density lipoprotein cholesterol levels (OR 1.07; 95% CI, 1.04-1.10), and elevated risk of T2DM (OR 1.04; 95%, CI 1.01-1.08). Conclusion Our study revealed an association between low CRP alleles in HNF1A and a high CVD risk, which indicated that antidiabetic drugs with CV benefits such as glucagon-like peptide-1 receptor agonists should be recommended as a first-line choice for HNF1A-MODY.