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CTLA-4 +49A/G and -318 C/T polymorphisms and cytokines level on inhibitors development of haemophilia A among different ethnicity in Malaysia

Introduction: Haemophilia A (HA) is an inherited X-chromosome recessive disorder characterized by the deficiency of factor VIII (FVIII). About 25-30% of HA patients which received FVIII concentrate developed inhibitors towards FVIII. Ethnicity has been associated as a predisposing factor for the for...

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Main Authors: Nadarajan, Anantha Kummar, KN Vaiappuri, VS Selvavani, Karim, Faraizah, Abu Bakar, Suhaili, Md Noor, Sabariah
Format: Article
Language:English
Published: Faculty of Medicine and Health Sciences, Universiti Putra Malaysia 2022
Online Access:http://psasir.upm.edu.my/id/eprint/99290/1/2022121911193801_MJMHS_0765.pdf
http://psasir.upm.edu.my/id/eprint/99290/
https://medic.upm.edu.my/upload/dokumen/2022121911193801_MJMHS_0765.pdf
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spelling my.upm.eprints.992902023-03-06T03:48:32Z http://psasir.upm.edu.my/id/eprint/99290/ CTLA-4 +49A/G and -318 C/T polymorphisms and cytokines level on inhibitors development of haemophilia A among different ethnicity in Malaysia Nadarajan, Anantha Kummar KN Vaiappuri, VS Selvavani Karim, Faraizah Abu Bakar, Suhaili Md Noor, Sabariah Introduction: Haemophilia A (HA) is an inherited X-chromosome recessive disorder characterized by the deficiency of factor VIII (FVIII). About 25-30% of HA patients which received FVIII concentrate developed inhibitors towards FVIII. Ethnicity has been associated as a predisposing factor for the formation of FVIII inhibitors. This study character- izes the polymorphism of +49A/G and -318C/T of Cytotoxic T-Lymphocytes Antigen 4 (CTLA-4) which relates to the development of inhibitors among Malaysian HA patients of Malay, Chinese and Indian ethnicity. Cytokines level of tumour necrosis factor alpha (TNFα), interleukin 4 (IL-4) and interleukin 10 (IL-10) were also measured to assess the link to inhibitors development. Method: Severe HA patients with and without inhibitor who were being treated at the National Blood Centre, Kuala Lumpur were recruited and consented where their collected blood was genotyped for both polymorphisms using the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) and their cytokines levels were measured using the Enzyme-linked Immunosorbent Assay (ELISA). Results: Analysis of the total 64 respondents who fulfilled the study criteria found polymorphisms of CTLA-4 +49A/G and CTLA-4 -318C/T were not significantly different among patients with and without inhibitors. However, HA patients without inhibitors revealed that the Chinese population exhibited a higher +49G allele which is protective towards inhibitors development. Indian patients expressed a higher level of inhibitors titre. Patients without inhibitors showed statistical differences between ethnicity for both genotypes and allele frequencies of CTLA-4 +49A/G (P < 0.05). Conclusion: The mixed pattern of polymorphisms and cytokine profiles were observed in multi-ethnicity. This finding requires further verification with a larger sample size involving multicenter for further confirmation. Faculty of Medicine and Health Sciences, Universiti Putra Malaysia 2022-12 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/99290/1/2022121911193801_MJMHS_0765.pdf Nadarajan, Anantha Kummar and KN Vaiappuri, VS Selvavani and Karim, Faraizah and Abu Bakar, Suhaili and Md Noor, Sabariah (2022) CTLA-4 +49A/G and -318 C/T polymorphisms and cytokines level on inhibitors development of haemophilia A among different ethnicity in Malaysia. Malaysian Journal of Medicine and Health Sciences, 18 (supp.21). pp. 2-8. ISSN 2636-9346 https://medic.upm.edu.my/upload/dokumen/2022121911193801_MJMHS_0765.pdf 10.47836/mjmhs18.s21.2
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description Introduction: Haemophilia A (HA) is an inherited X-chromosome recessive disorder characterized by the deficiency of factor VIII (FVIII). About 25-30% of HA patients which received FVIII concentrate developed inhibitors towards FVIII. Ethnicity has been associated as a predisposing factor for the formation of FVIII inhibitors. This study character- izes the polymorphism of +49A/G and -318C/T of Cytotoxic T-Lymphocytes Antigen 4 (CTLA-4) which relates to the development of inhibitors among Malaysian HA patients of Malay, Chinese and Indian ethnicity. Cytokines level of tumour necrosis factor alpha (TNFα), interleukin 4 (IL-4) and interleukin 10 (IL-10) were also measured to assess the link to inhibitors development. Method: Severe HA patients with and without inhibitor who were being treated at the National Blood Centre, Kuala Lumpur were recruited and consented where their collected blood was genotyped for both polymorphisms using the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) and their cytokines levels were measured using the Enzyme-linked Immunosorbent Assay (ELISA). Results: Analysis of the total 64 respondents who fulfilled the study criteria found polymorphisms of CTLA-4 +49A/G and CTLA-4 -318C/T were not significantly different among patients with and without inhibitors. However, HA patients without inhibitors revealed that the Chinese population exhibited a higher +49G allele which is protective towards inhibitors development. Indian patients expressed a higher level of inhibitors titre. Patients without inhibitors showed statistical differences between ethnicity for both genotypes and allele frequencies of CTLA-4 +49A/G (P < 0.05). Conclusion: The mixed pattern of polymorphisms and cytokine profiles were observed in multi-ethnicity. This finding requires further verification with a larger sample size involving multicenter for further confirmation.
format Article
author Nadarajan, Anantha Kummar
KN Vaiappuri, VS Selvavani
Karim, Faraizah
Abu Bakar, Suhaili
Md Noor, Sabariah
spellingShingle Nadarajan, Anantha Kummar
KN Vaiappuri, VS Selvavani
Karim, Faraizah
Abu Bakar, Suhaili
Md Noor, Sabariah
CTLA-4 +49A/G and -318 C/T polymorphisms and cytokines level on inhibitors development of haemophilia A among different ethnicity in Malaysia
author_facet Nadarajan, Anantha Kummar
KN Vaiappuri, VS Selvavani
Karim, Faraizah
Abu Bakar, Suhaili
Md Noor, Sabariah
author_sort Nadarajan, Anantha Kummar
title CTLA-4 +49A/G and -318 C/T polymorphisms and cytokines level on inhibitors development of haemophilia A among different ethnicity in Malaysia
title_short CTLA-4 +49A/G and -318 C/T polymorphisms and cytokines level on inhibitors development of haemophilia A among different ethnicity in Malaysia
title_full CTLA-4 +49A/G and -318 C/T polymorphisms and cytokines level on inhibitors development of haemophilia A among different ethnicity in Malaysia
title_fullStr CTLA-4 +49A/G and -318 C/T polymorphisms and cytokines level on inhibitors development of haemophilia A among different ethnicity in Malaysia
title_full_unstemmed CTLA-4 +49A/G and -318 C/T polymorphisms and cytokines level on inhibitors development of haemophilia A among different ethnicity in Malaysia
title_sort ctla-4 +49a/g and -318 c/t polymorphisms and cytokines level on inhibitors development of haemophilia a among different ethnicity in malaysia
publisher Faculty of Medicine and Health Sciences, Universiti Putra Malaysia
publishDate 2022
url http://psasir.upm.edu.my/id/eprint/99290/1/2022121911193801_MJMHS_0765.pdf
http://psasir.upm.edu.my/id/eprint/99290/
https://medic.upm.edu.my/upload/dokumen/2022121911193801_MJMHS_0765.pdf
_version_ 1759690994883756032
score 13.211869

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