Perforin gene mutations in patients with acquired severe aplastic anemia.
- Author:
Jian ZHANG
1
;
Rong FU
;
Jun WANG
;
Li-Juan LI
;
Jia SONG
;
Wen QU
;
Hua-Quan WANG
;
Li-Min XING
;
Hong LIU
;
Yu-Hong WU
;
Jin GUAN
;
Guo-Jin WANG
;
Xiao-Min WANG
;
Yong LIANG
;
Er-Bao RUAN
;
Hui LIU
;
Zong-Hong SHAO
Author Information
1. Department of Hematoloy and Oncology, Tianjin Medical University General Hospital, Tianjin 300052, China.
- Publication Type:Journal Article
- MeSH:
Adolescent;
Adult;
Aged;
Anemia, Aplastic;
genetics;
Base Sequence;
Case-Control Studies;
Child;
Child, Preschool;
Female;
Genetic Predisposition to Disease;
Heterozygote;
Humans;
Male;
Middle Aged;
Mutation;
Perforin;
Pore Forming Cytotoxic Proteins;
genetics;
Young Adult
- From:
Journal of Experimental Hematology
2011;19(2):431-434
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to explore whether the perforin gene 1 (PRF1) mutation is the basis of genetic susceptibility to pathogenesis of acquired severe aplastic anemia (SAA). DNA exon2 and exon3 of PRF1 gene in peripheral blood mononuclear cells in 31 SAA patients and 15 normal controls were amplified by PCR; the sequencing was performed by using ABI pRISM 373OXL sequencer; the mutation loci were sought through checking sequences with GenBank-reported sequences; after the mutation sequences were found, those were cloned into M13 phage vector, then the corresponding sequences of gained 2 chromosomes were sequenced respectively to determine the distribution of different mutations on chromosomes. The results showed that (1) one homozygous mutation (822 C > T, synonymous mutation) and one heterozygous mutation (907 G > A, methionine 303 valine) were found in PRF1 coding region of 2 SAA patients. These mutations were not detected in normal controls. (2) 1 SNP (rs885822) in the coding region was detected in SAA patients and controls, and the heterozygosity rate between the 2 groups was different (p < 0.05). It is concluded that perforin gene mutation may be one risk factor in the aberrant proliferation and activation of cytotoxic T cells in pathogenesis of a part of patients with aplastic anemia.
