Paper
Objective: Rare variants in HNF1A account for Maturity onset diabetes of the young 3 (MODY3). Common variants of HNF1A are associated with serum CRP, and MODY3 patients have greatly low CRP levels distinct from other types of diabetes. Low dose sulfonylureas are recommended for MODY3 patients in ADA guideline. However, available clinical trial showed liraglutide, an anti-diabetic drug protecting from cardiovascular disease (CVD), had similar effect and lower risk of hypoglycemia compared with glimepiride. Since the common variants of HNF1A are associated with higher risk of CVD, we aimed to perform the meta-analysis to investigate the association of the low CRP alleles in HNF1A with CVD and indirectly evaluate the CVD risk of MODY3. Methods: A comprehensive literature search was conducted using PubMed, Embase and CNKI databases from inception to December 2023. Association studies concerning the association of HNF1A with CRP, CVD, blood lipid and diabetes were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using Review Manager 5.3. Results: Three common variants in the coding region of HNF1A (rs1169288, rs2464196, rs1169289) were included in our study. The minor alleles of these variants were all associated 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 1.05, 95%CI 1.04-1.06), elevated LDL cholesterol levels (OR 1.05, 95%Cl 1.03-1.08) and increased risk of type 2 diabetes (OR 1.04, 95%Cl 1.01-1.08). Conclusion: Our study has revealed an association between low CRP alleles in HNF1A and an elevated risk of CVD, possibly due to dyslipidemia or poor glycemic control. This suggests that for MODY3 patients, it may be more reasonable to prioritize anti-diabetic with cardiovascular protection such as GLP-1 receptor agonist, but not sulfonylureas. Disclosure C. Yang: None. X. Han: None. L. Ji: None.