Low C reactive protein-alleles in hepatocyte nuclear factor 1A are associated with an increased risk of cardiovascular disease: a Meta-analysis.

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, 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.

Data Sources: A literature search was performed using PubMed, Embase and Cochrane Library databases from inception to December 2023.

Study Selection: All relevant studies concerning the association of HNF1A with CRP, CVD, lipid and type 2 diabetes were included.

Data Extraction: Odds ratios (ORs), 95% confidence intervals (CIs) and study characteristics were extracted.

Data Synthesis: Three common coding variants of HNF1A (rs1169288, rs2464196, rs1169289) were examined. The minor alleles of these variants correlated with low CRP levels (OR 0.89, 95%Cl 0.86-0.91; OR 0.89, 95%Cl 0.88-0.91; OR 0.89, 95%Cl 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 LDL-cholesterol levels (OR 1.07, 95%CI 1.04-1.10) and elevated risk of type 2 diabetes (OR 1.04, 95%CI 1.01-1.08).

Conclusions: Our study revealed an association between low CRP-alleles in HNF1A and a high CVD risk, which indicated that anti-diabetic drugs with cardiovascular benefits such as GLP-1 receptor agonist should be recommended as first-line choice for HNF1A-MODY.