Cause Leukopenia. Ctla-4 Gene Polymorphism With Antithyroid Drugs Correlation

Objective To investigate the relationship between the leukopenia caused by ATD and two polymorphism sites in the CTLA-4 gene including the promoter region-318 site and the exon 1 position 49 site.Methods 211 patients with GD including 73 patients with leukopenia caused by ATD,86 patients without leukopenia caused by ATD,52 GD patients with leukopenia before using ATD.74 patients with leukopenia and without GD and 85 healthy controls were studied. The genotype and allele frequencies were assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results①Significant differences in genotype frequencies and allele frequencies were not observed in promoter region-318 site of CTLA-4 gene between GD group and control group (χ2=0.60, P=0.74;χ2=0.06, P=0.80)②Significant differences in promoter region-318 site of CTLA-4 gene were observed between the leukopenia caused by ATD and no leukopenia caused by ATD group (χ2=7-28, P=0.03;χ2=4.05, P=0.04),The CT+TT genotype frequency was significantly higher in the leukopenia caused by ATD group than that in no leukopenia caused by ATD group (26.0% vs 11.6%).The T allele frequency was significantly higher in leukopenia caused by ATD group than that in no leukopenia caused by ATD group (13.0% vs 6.4%)③Significant differences in promoter region-318 site of CTLA-4 gene were not observed between leukopenia caused by ATD group and leukopenia before use ATD group(χ2=2.91,P=0.09;χ2=2.57, P=0.11).In CTLA-4 gene exon 1 position 49 site①Significant differences in genotype frequencies and allele frequencies were observed between GD and control group (χ2=17.74, P=0.0001; x2=6.48, P=0.01);②Significant differences in genotype frequencies and allele frequencies were not observed between the leukopenia caused by ATD group and no leukopenia caused by ATD group (χ2=0.28, P=0.87;χ2=0.01,P=0.91);③Significant differences in genotype frequencies and allele frequencies were not observed between leukopenia caused by ATD group and leukopenia before use ATD group (χ2=0.15, P=0.93;χ2=0.39, P=0.53);④Significant differences in genotype frequencies and allele frequencies were not observed between leukopenia with GD and leukopenia without GD group (χ2=5.49, P=0.06;χ2=0.42, P=0.52)Conclusion The polymorphism of T allele in CTLA-4 gene promoter region-318 site in Shandong Qingdao Han population is associated with the leukopenia caused by ATD, although is not associated with the susceptibility to the development of GD. The polymorphism of A allele in CTLA-4 gene exon 1 position 49 site is not associated with the leukopenia caused by ATD in Shandong Qingdao Han population,but is associated with the susceptibility to the development of GD.