Association of CD40 gene polymorphisms and immune thrombocytopenic purpura in the adult Egyptian population

Hend Nabil Ellithy; Sherif Mohamed Yousry; Asmaa Abdel-Aal; Lelian Tawadros; Nouran Momen

doi:10.5045/br.2022.2022057

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Blood Res 2022; 57(3):

Published online September 30, 2022

https://doi.org/10.5045/br.2022.2022057

Association of CD40 gene polymorphisms and immune thrombocytopenic purpura in the adult Egyptian population

Hend Nabil Ellithy¹, Sherif Mohamed Yousry², Asmaa Abdel-Aal², Lelian Tawadros², Nouran Momen²

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¹Clinical Hematology Unit-Internal Medicine Department, ²Clinical and Chemical Pathology Department, Kasr Al Ainy Faculty of Medicine, Cairo University, Cairo, Egypt

Correspondence to : Hend Nabil Ellithy, M.D.
Clinical Hematology Unit-Internal Medicine Department, Kasr Al Ainy Faculty of Medicine, Cairo University, Cairo 4240310, Egypt
E-mail: hend.allithy@kasraliny.edu.eg

Received: March 4, 2022; Revised: April 15, 2022; Accepted: July 28, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Abstract

Background
The pathophysiology underlying primary adult immune thrombocytopenic purpura (ITP) has not yet been identified. However, many mechanisms affect the immune system, causing defective tolerance to self-platelets and megakaryocytes. Cluster of differentiation 40 (CD40) contributes to both humoral and cell-mediated immune responses.
Methods
This case‒control study was conducted to detect rs4810485G>T and rs1883832C>T polymorphisms of CD40 in Egyptian patients with persistent/chronic ITP to clarify their possible association with chronic disease evolution. This study included 50 patients with persistent/chronic ITP and 50 healthy controls. Genotyping was performed using the polymerase chain reaction‒restriction fragment length polymorphism technique.
Results
Genotyping of rs1883832 and rs4810485 revealed no statistically significant differences between the two groups. However, combined gene polymorphism genotyping showed a statistically significant difference between the two groups (P<0.01).
Conclusion
Our results indicate a strong association between the combined polymorphism of both genes and susceptibility to developing ITP among adult Egyptian patients. Targeting this pathway using novel therapeutic approaches is promising.

Keywords CD40, rs1883832, rs4810485, Polymorphism, Chronic ITP

Article

Original Article

Blood Res 2022; 57(3): 229-234

Published online September 30, 2022 https://doi.org/10.5045/br.2022.2022057

Association of CD40 gene polymorphisms and immune thrombocytopenic purpura in the adult Egyptian population

Hend Nabil Ellithy¹, Sherif Mohamed Yousry², Asmaa Abdel-Aal², Lelian Tawadros², Nouran Momen²

¹Clinical Hematology Unit-Internal Medicine Department, ²Clinical and Chemical Pathology Department, Kasr Al Ainy Faculty of Medicine, Cairo University, Cairo, Egypt

Correspondence to:Hend Nabil Ellithy, M.D.
Clinical Hematology Unit-Internal Medicine Department, Kasr Al Ainy Faculty of Medicine, Cairo University, Cairo 4240310, Egypt
E-mail: hend.allithy@kasraliny.edu.eg

Received: March 4, 2022; Revised: April 15, 2022; Accepted: July 28, 2022

Abstract

Keywords: CD40, rs1883832, rs4810485, Polymorphism, Chronic ITP

Abstract

Fig 1.

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Figure 1.Agarose gel electrophoresis of the rs1883832 gene PCR products. Enzyme digestion products of rs1883832 using NcoI restriction enzyme showing the following: Lane 6: Wild GG genotype showing one band at 503 bp. Lanes 2, 3, 4, 7, 8, 9, and 10: Heterozygous AG genotype showing three bands at 503 bp, 130 bp, and 373 bp, respectively. Lanes 1 and 5: Homozygous AA genotype showing two bands at 130 bp and 373 bp, respectively.
Abbreviation: M, DNA marker.

Blood Research 2022; 57: 229-234https://doi.org/10.5045/br.2022.2022057

Fig 2.

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Figure 2.Agarose gel electrophoresis of the rs4810485 gene PCR products. The enzyme digestion products of rs4810485 using MspI restriction enzyme showing the following: Lane 2: Wild GG genotype showing one band at 288 bp. Lanes 1, 3, 5, 6, 7, 8, and 9: Homozygous TT genotype showing two bands at 104 bp and 184 bp, respectively. Lanes 4 and 10: Heterozygous GT genotype showing three bands at 288 bp, 104 bp, and 184 bp, respectively.
Abbreviation: M, DNA marker.

Blood Research 2022; 57: 229-234https://doi.org/10.5045/br.2022.2022057

Table 1 . Clinical and laboratory data of 50 patients with ITP..

Variable	Value (N=50)
Sex, N (%)
Male	5 (10%)
Female	45 (90%)
Age at sampling, years
Mean±SD, range	30.6±11.12 (14–60)
Platelets at sampling ×10⁹/L, N (%)
Platelet count <20×10⁹/L	36 (72%)
Platelet count >20×10⁹/L	14 (28%)
Bleeding tendency at time of initial diagnosis, N (%)
No bleeding	0 (0%)
Skin bleeding	43 (86%)
Mucosal bleeding	31 (62%)
GIT or GUT bleeding	40 (80%)
Disease state at sampling, N (%)
Activity	50 (100%)
Remission	0 (0%)
Disease severity at sampling, N (%)
Bleeder	4 (8%)
Non-bleeder	46 (92%)
Treatment regimen, N (%)
No treatment (under observation)	0 (0%)
Corticosteroids (alone or in combination)	50 (100%)
Azathioprine (in different combinations)	30 (60%)
TPO-RA	4 (8%)
Splenectomy	0 (0%)
Treatment response, N (%)
Complete response	35 (70%)
Response	14 (28%)
No response	1 (2%)
Refractory	0 (0%)

Table 2 . Comparison between patients with persistent/chronic ITP and the control group regarding combined gene polymorphism..

Item	ITP group (N=50)	Control group (N=50)	P
Combined rs1883832 (C>T) and rs4810485 (G>T) gene polymorphism
CC-GG	4 (8%)	0 (0%)	<0.001^a)
TT-TT	22 (44%)	14 (28%)
CT-GT	24 (48%)	8 (16%)
TT-GG	0 (0%)	0 (0%)
CC-GT	0 (0%)	2 (4%)
TT-GT	0 (0%)	6 (12%)
CC-TT	0 (0%)	0 (0%)
CT-TT	0 (0%)	16 (32%)
CT-GG	0 (0%)	2 (4%)

^a)P-values of <0.001 were considered highly statistically significant..

Table 3 . Comparison between completely responsive, responsive, and nonresponsive patients with ITP regarding rs4810485 (G>T) and rs1883832 (C>T) gene polymorphisms..

Item	Completely responsive	Responsive	Nonresponsive	P
rs4810485 (G>T) gene polymorphism, N (%)
rs4810485 gene polymorphism, N (%)
Wild GG genotype	3 (75%)	1 (25%)	0 (0%)	0.439
Heterozygous GT genotype	15 (62.5%)	9 (37.5)	0 (0%)
Homozygous TT genotype	17 (77.3%)	4 (18.2%)	1 (4.5%)
G allele	21 (55.3%)	11 (73.3%)	0 (0%)	0.230
T allele	49 (94.2%)	17 (94.4%)	2 (100%)	0.941
rs1883832 (C>T) gene polymorphism, N (%)
gene polymorphism, N (%)
Wild CC genotype	3 (75%)	1 (25%)	0 (0%)	0.439
Heterozygous CT genotype	15 (62.5%)	9 (37.5)	0 (0%)
Homozygous TT genotype	17 (77.3%)	4 (18.2%)	1 (4.5%)
C allele	21 (55.3%)	11 (73.3%)	0 (0%)	0.230
T allele	49 (94.2%)	17 (94.4%)	2 (100%)	0.941

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Association of CD40 gene polymorphisms and immune thrombocytopenic purpura in the adult Egyptian population

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Association of CD40 gene polymorphisms and immune thrombocytopenic purpura in the adult Egyptian population

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