PAX4 gene polymorphism and islet autoantibody-negative ketosis-prone diabetes / 中南大学学报(医学版)

ABSTRACT

Objective To investigate PAX4 gene polymorphism and its association with islet autoantibody-negative patients with ketosis-prone diabetes in Chinese Han population. Methods We screened the variation of exon 3 and 9 within PAX4 gene by denaturing high performance liquid chromatography(DHPLC) in 112 non-diabetes control subjects (NC group) and 141 patients with ketosis-prone diabetes (KPD group), who were both negative for glutamic acid decarboxylase antibody (GAD-Ab) as well as protein tyrosine phosphatase antibody (IA-2Ab) . The sequences of abnormal peaks were analyzed by DNA-sequencing. The A1168C single nucleotide polymorphism in PAX4 gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 308 non-diabetic control subjects and 141 KPD patients. Results No variation was discovered in PAX4 gene exon 3 both in the patients and in the controls. There was a single nucleotide polymorphism locus A1168C in the PAX4 gene exon 9, which induced mis-sence mutation P321H(rs712701). No significant difference was observed in the genotype and allele frequencies of A1168C polymorphism between KPD patients and control subjects (P=0.532, 0.426). The difference was detected in the CC genotype and C allele frequencies in the KPD group when patients were stratified by gender (P=0.009,0.028). According to age at diagnosis, the difference was observed in the CC genotype and C allele frequencies between <20 years old and ≥20 years old in the KPD group (P=0.034,0.032). The level of FCP in the CC genotype group was significantly higher than that of FCP in AA genotype group (P=0.005). Conclusion A1168C polymorphism in PAX4 gene may not play an essential role in the genetic susceptibility of the islet autoantibody-negative KPD in Chinese Han population. However, A1168C variation may contribute to the predisposition to the male or <20 years old patients with islet autoantibody-negative KPD.