Correlations between growth differentiation factor 15 (GDF-15) serum levels and gene polymorphism with type 2 diabetes mellitus

Purpose: To date, the relationship between Growth Differentiation Factor 15 (GDF-15) gene polymorphism and the risk of type 2 diabetes mellitus (T2DM) has not been clarified. Our study aims to explore the association between serum GDF-15 levels and related gene polymorphism with the risk of T2DM in a Chinese rural Yao population. Methods: This was a 1:1 case-control study with 179 T2DM patients and 179 age- and sex-matched control participants. Serum GDF-15 levels were measured by enzyme-linked immunosorbent assay, and polymorphisms (rs1059519, rs1059369, rs1804826 and rs1054564) were genotyped by MassArray mass spectrometry. Results: Serum GDF-15 (sGDF-15) levels were higher in patients with T2DM and glycosylated hemoglobin (HbA1c) >= 6.5 % compared to that in controls (p < 0.001). The area under the curve (AUC) corresponding to sGDF-15 levels was 0.626. Serum GDF-15 was positively correlated with fasting plasma glucose (FPG) (rs = 0.150, p < 0.001) and HbA1c (rs = 0.160, p < 0.001). The frequency of GDF-15 gene rs1054564 GC + CC genotype was significantly associated with increased risk of T2DM compared to GG genotype (OR = 1.724, 95CI: 1.046-2.841, p = 0.033). Frequencies of rs1804826 T allele (beta additive = 113.318, p = 0.026) and rs1054564 C allele (beta additive = 247.282, p = 0.001, beta dominant = 286.109, p = 0.001) was significantly correlated with higher sGDF-15. The rs1059519 C allele was negatively correlated with FPG ( beta recessive = -0.607, p = 0.047) and HbA1c ( beta recessive = -0.456, p = 0.020). Conclusion: Serum GDF-15 levels were positively correlated with FPG and HbA1c. The GDF-15 rs1054564 GC + CC genotype was associated with a significantly higher T2DM risk. The rs1059519 C allele was negatively correlated with FPG and HbA1c.