POLYMORPHISM OF THE COMPLEMENT RECEPTOR 1 GENE IN CHINESE PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
(Abstract release date: 05/19/16)
EHA Library. Han B. 06/09/16; 132558; E1009
Dr. Bing Han
Contributions
Contributions
Abstract
Abstract: E1009
Type: Eposter Presentation
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired genetic disorder of the bone marrow, eculizumab is an effective monoclonal antibody inhibits terminal complement activation through block the distal complement pathway, but the hematologic response to eculizumab is variable. Previous report showed patients with PNH who have rare allele (L) of the complement receptor 1 (CR1) gene, either heterozygotes (H/L) or homozygotes (L/L), displayed more sub-optimal responder to eculizumab compared with common allele (H/H).
Aims
We investigate polymorphism of the CR1 gene in Chinese patients with PNH in order to determine its potential impact on eculizumab efficiency.
Methods
DNA was extracted from peripheral blood mononuclear cells from 95 Chinese patients with PNH. Rs2274567 and rs3811381 in CR1 gene were genotyped by polymerase chain reaction fragment length polymorphism methods ( PCR-RFLP ). Hemolysis factors including hemoglobin level and LDH level were investigated and thrombotic percentage was evaluated between different genotypes.
Results
Of the 95 patients, frequencies of the rare rs2274567 allele (12%) is much lower than Caucasian PNH population previous reported (31%, P<0.0001), and rare allele frequencies of rs3811381 is also significantly lower (12% vs 29%, P<0.0001) in Chinese patients. 72(76%) patients were H/H, while 23(24%) patients were H/L genotype for rs2274567 polymorphism. There were no difference between the two genotypes in hemoglobin level (83.7 g/L vs 72.8 g/L, p=0. 0917) and LDH level (1312U/L vs 1022 U/L, p=0.2682). As for the rs3811381 genotype, there were 71(75%), 22 (23%) and 2 (2.1%) patients with H/H, H/L, L/L genotype separately. There was no difference among the different genotype groups in the hemoglobin level (83.2g/L, 74.8g/L and 75.5 g/L, respectively, p=0.4278) and LDH level (1312 U/L, 997 U/L,1233 U/L, respectively, p=0.5171 ), either. Although not significantly, the thrombotic percentage tent to increase from H/H to H/L ( 17% to 30%, p=0.2288 ) for rs2274567 polymorphism and H/H to H/L to L/L genotype (17%, 27%, 50%, respectively, p=0.3201) for rs3811381 genotype.
Conclusion
Very rare H/L or L/L genotype of CR1 was found in Chinese people with PNH. Frequencies of Chinese rare alleles in CR1 gene were significantly lower than that of Caucasian population, which may indicate a favorable response to eculizumab treatment. No difference of hemoglobin level or hemolysis was found among different genotype groups, but the percentage of thrombosis seemed to increase from H/H, H/L to L/L.
Session topic: E-poster
Keyword(s): Complement, Gene polymorphism, PNH
Type: Eposter Presentation
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired genetic disorder of the bone marrow, eculizumab is an effective monoclonal antibody inhibits terminal complement activation through block the distal complement pathway, but the hematologic response to eculizumab is variable. Previous report showed patients with PNH who have rare allele (L) of the complement receptor 1 (CR1) gene, either heterozygotes (H/L) or homozygotes (L/L), displayed more sub-optimal responder to eculizumab compared with common allele (H/H).
Aims
We investigate polymorphism of the CR1 gene in Chinese patients with PNH in order to determine its potential impact on eculizumab efficiency.
Methods
DNA was extracted from peripheral blood mononuclear cells from 95 Chinese patients with PNH. Rs2274567 and rs3811381 in CR1 gene were genotyped by polymerase chain reaction fragment length polymorphism methods ( PCR-RFLP ). Hemolysis factors including hemoglobin level and LDH level were investigated and thrombotic percentage was evaluated between different genotypes.
Results
Of the 95 patients, frequencies of the rare rs2274567 allele (12%) is much lower than Caucasian PNH population previous reported (31%, P<0.0001), and rare allele frequencies of rs3811381 is also significantly lower (12% vs 29%, P<0.0001) in Chinese patients. 72(76%) patients were H/H, while 23(24%) patients were H/L genotype for rs2274567 polymorphism. There were no difference between the two genotypes in hemoglobin level (83.7 g/L vs 72.8 g/L, p=0. 0917) and LDH level (1312U/L vs 1022 U/L, p=0.2682). As for the rs3811381 genotype, there were 71(75%), 22 (23%) and 2 (2.1%) patients with H/H, H/L, L/L genotype separately. There was no difference among the different genotype groups in the hemoglobin level (83.2g/L, 74.8g/L and 75.5 g/L, respectively, p=0.4278) and LDH level (1312 U/L, 997 U/L,1233 U/L, respectively, p=0.5171 ), either. Although not significantly, the thrombotic percentage tent to increase from H/H to H/L ( 17% to 30%, p=0.2288 ) for rs2274567 polymorphism and H/H to H/L to L/L genotype (17%, 27%, 50%, respectively, p=0.3201) for rs3811381 genotype.
Conclusion
Very rare H/L or L/L genotype of CR1 was found in Chinese people with PNH. Frequencies of Chinese rare alleles in CR1 gene were significantly lower than that of Caucasian population, which may indicate a favorable response to eculizumab treatment. No difference of hemoglobin level or hemolysis was found among different genotype groups, but the percentage of thrombosis seemed to increase from H/H, H/L to L/L.
Session topic: E-poster
Keyword(s): Complement, Gene polymorphism, PNH
Abstract: E1009
Type: Eposter Presentation
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired genetic disorder of the bone marrow, eculizumab is an effective monoclonal antibody inhibits terminal complement activation through block the distal complement pathway, but the hematologic response to eculizumab is variable. Previous report showed patients with PNH who have rare allele (L) of the complement receptor 1 (CR1) gene, either heterozygotes (H/L) or homozygotes (L/L), displayed more sub-optimal responder to eculizumab compared with common allele (H/H).
Aims
We investigate polymorphism of the CR1 gene in Chinese patients with PNH in order to determine its potential impact on eculizumab efficiency.
Methods
DNA was extracted from peripheral blood mononuclear cells from 95 Chinese patients with PNH. Rs2274567 and rs3811381 in CR1 gene were genotyped by polymerase chain reaction fragment length polymorphism methods ( PCR-RFLP ). Hemolysis factors including hemoglobin level and LDH level were investigated and thrombotic percentage was evaluated between different genotypes.
Results
Of the 95 patients, frequencies of the rare rs2274567 allele (12%) is much lower than Caucasian PNH population previous reported (31%, P<0.0001), and rare allele frequencies of rs3811381 is also significantly lower (12% vs 29%, P<0.0001) in Chinese patients. 72(76%) patients were H/H, while 23(24%) patients were H/L genotype for rs2274567 polymorphism. There were no difference between the two genotypes in hemoglobin level (83.7 g/L vs 72.8 g/L, p=0. 0917) and LDH level (1312U/L vs 1022 U/L, p=0.2682). As for the rs3811381 genotype, there were 71(75%), 22 (23%) and 2 (2.1%) patients with H/H, H/L, L/L genotype separately. There was no difference among the different genotype groups in the hemoglobin level (83.2g/L, 74.8g/L and 75.5 g/L, respectively, p=0.4278) and LDH level (1312 U/L, 997 U/L,1233 U/L, respectively, p=0.5171 ), either. Although not significantly, the thrombotic percentage tent to increase from H/H to H/L ( 17% to 30%, p=0.2288 ) for rs2274567 polymorphism and H/H to H/L to L/L genotype (17%, 27%, 50%, respectively, p=0.3201) for rs3811381 genotype.
Conclusion
Very rare H/L or L/L genotype of CR1 was found in Chinese people with PNH. Frequencies of Chinese rare alleles in CR1 gene were significantly lower than that of Caucasian population, which may indicate a favorable response to eculizumab treatment. No difference of hemoglobin level or hemolysis was found among different genotype groups, but the percentage of thrombosis seemed to increase from H/H, H/L to L/L.
Session topic: E-poster
Keyword(s): Complement, Gene polymorphism, PNH
Type: Eposter Presentation
Background
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired genetic disorder of the bone marrow, eculizumab is an effective monoclonal antibody inhibits terminal complement activation through block the distal complement pathway, but the hematologic response to eculizumab is variable. Previous report showed patients with PNH who have rare allele (L) of the complement receptor 1 (CR1) gene, either heterozygotes (H/L) or homozygotes (L/L), displayed more sub-optimal responder to eculizumab compared with common allele (H/H).
Aims
We investigate polymorphism of the CR1 gene in Chinese patients with PNH in order to determine its potential impact on eculizumab efficiency.
Methods
DNA was extracted from peripheral blood mononuclear cells from 95 Chinese patients with PNH. Rs2274567 and rs3811381 in CR1 gene were genotyped by polymerase chain reaction fragment length polymorphism methods ( PCR-RFLP ). Hemolysis factors including hemoglobin level and LDH level were investigated and thrombotic percentage was evaluated between different genotypes.
Results
Of the 95 patients, frequencies of the rare rs2274567 allele (12%) is much lower than Caucasian PNH population previous reported (31%, P<0.0001), and rare allele frequencies of rs3811381 is also significantly lower (12% vs 29%, P<0.0001) in Chinese patients. 72(76%) patients were H/H, while 23(24%) patients were H/L genotype for rs2274567 polymorphism. There were no difference between the two genotypes in hemoglobin level (83.7 g/L vs 72.8 g/L, p=0. 0917) and LDH level (1312U/L vs 1022 U/L, p=0.2682). As for the rs3811381 genotype, there were 71(75%), 22 (23%) and 2 (2.1%) patients with H/H, H/L, L/L genotype separately. There was no difference among the different genotype groups in the hemoglobin level (83.2g/L, 74.8g/L and 75.5 g/L, respectively, p=0.4278) and LDH level (1312 U/L, 997 U/L,1233 U/L, respectively, p=0.5171 ), either. Although not significantly, the thrombotic percentage tent to increase from H/H to H/L ( 17% to 30%, p=0.2288 ) for rs2274567 polymorphism and H/H to H/L to L/L genotype (17%, 27%, 50%, respectively, p=0.3201) for rs3811381 genotype.
Conclusion
Very rare H/L or L/L genotype of CR1 was found in Chinese people with PNH. Frequencies of Chinese rare alleles in CR1 gene were significantly lower than that of Caucasian population, which may indicate a favorable response to eculizumab treatment. No difference of hemoglobin level or hemolysis was found among different genotype groups, but the percentage of thrombosis seemed to increase from H/H, H/L to L/L.
Session topic: E-poster
Keyword(s): Complement, Gene polymorphism, PNH
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