Abstract: Objective To investigate and analyze the relationship between GCK gene polymorphism and steroid diabetes (SD) in patients with primary nephrotic syndrome treated with glucocorticoid. Methods From January 2015 to December 2019, 148 patients with primary urinary nephrotic syndrome were continuously recruited, and they received glucocorticoid-induced immunotherapy. DNA was extracted from the subjects' blood samples, and the association between rs13306388, rs2971672 and rs1799884 in the GCK gene region and SD was analyzed. Results The total incidence of SD in all subjects was 35.1% (52/148). The subjects in the SD group were older than those in the non-SD group (P<0.001), and the glucocorticoid concentration/dose was higher (P<0.05). The genotype distribution of all SNPs was Hardy-Weinberg equilibrium (P>0.05). Among the allele frequencies of GCK polymorphism, only the rs2971672*C allele was significantly correlated with the occurrence of SD (OR=0.37; 95%CI=0.16 to 0.80; P=0.012). After adjusting for age in multiple logistic regression analysis, the SNP of GCK genotype rs1799884 (codominant 2 model: OR=3.63, 95% CI=1.19~12.06, P=0.027; recessive model: OR=3.78, 95% CI=1.22~11.94, P=0.035) and SNP rs2971672 (commonly dominant 1 model: OR=0.32, 95%CI=0.13~0.75, P=0.009; dominant model: OR=0.29, 95%CI= 0.12~0.68 , P=0.002) is significantly related to the occurrence of SD. Conclusion The mutations at rs2971672 and rs1799884 in the GCK gene region may affect the occurrence of SD events in primary nephrotic syndrome receiving glucocorticoid immunosuppressive therapy.

Key words: Glucocorticoid, Diabetes, Single nucleotide polymorphism, Glucokinase, Nephrotic syndrome