Evidence of new intragenic HBB haplotypes model for the prediction of beta-thalassemia in the Malaysian population
Abstract This study sought to determine the potential role of HBB haplotypes to predict beta-thalassemia in the Malaysian population. A total of 543 archived samples were selected for this study. Five tagging SNPs in the beta-globin gene (HBB; NG_000007.3) were analyzed for SNP-based and haplotype a...
Guardado en:
| Autores principales: | , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/b6f83b202f7944819ba8a21e16708e7e |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:b6f83b202f7944819ba8a21e16708e7e |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:b6f83b202f7944819ba8a21e16708e7e2021-12-02T17:08:43ZEvidence of new intragenic HBB haplotypes model for the prediction of beta-thalassemia in the Malaysian population10.1038/s41598-021-96018-y2045-2322https://doaj.org/article/b6f83b202f7944819ba8a21e16708e7e2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96018-yhttps://doaj.org/toc/2045-2322Abstract This study sought to determine the potential role of HBB haplotypes to predict beta-thalassemia in the Malaysian population. A total of 543 archived samples were selected for this study. Five tagging SNPs in the beta-globin gene (HBB; NG_000007.3) were analyzed for SNP-based and haplotype association using SHEsis online software. Single-SNP-based association analysis showed three SNPs have a statistically significant association with beta-thalassemia. When Bonferroni correction was applied, four SNPs were found statistically significant with beta-thalassemia; IVS2-74T>G (p adj = 0.047), IVS2-16G>C (p adj = 0.017), IVS2-666C>T (p adj = 0.017) and 3’UTR + 314G>A (p adj = 0.002). However, 3'UTR + 233G>C did not yield a significant association with p adj value = 0.076. Further investigation using combined five SNPs for haplotype association analysis revealed three susceptible haplotypes with significant p values of which, haplotypes 1-2-2-1-1 (p = 6.49 × 10−7, OR = 10.371 [3.345–32.148]), 1-2-1-1-1 (p = 0.009, OR = 1.423 [1.095–1.850] and 1-1-1-1-1 (p = 1.39 × 10−4, OR = 10.221 [2.345–44.555]). Three haplotypes showed protective effect with significant p value of which, 2-2-1-1-1 (p = 0.006, OR = 0.668 [0.500–0.893]), 1-1-2-2-1 (p = 0.013, OR = 0.357 [0.153–0.830]) and 1-1-2-1-1 (p = 0.033, OR = 0.745 [0.567–0.977]). This study has identified the potential use of intragenic polymorphic markers in the HBB gene, which were significantly associated with beta-thalassemia. Combining these five SNPs defined a new haplotype model for beta-thalassemia and further evaluation for predicting severity in beta-thalassemia.Nur-Aisyah AzizWan-Rohani Wan TaibNur-Khairunnisa KharolazamanImilia IsmailHamid Ali Nagi Al-JamalNadiah Wan-Arfah Wan Abdul JamilEzalia EsaHishamshah IbrahimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-6 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Nur-Aisyah Aziz Wan-Rohani Wan Taib Nur-Khairunnisa Kharolazaman Imilia Ismail Hamid Ali Nagi Al-Jamal Nadiah Wan-Arfah Wan Abdul Jamil Ezalia Esa Hishamshah Ibrahim Evidence of new intragenic HBB haplotypes model for the prediction of beta-thalassemia in the Malaysian population |
| description |
Abstract This study sought to determine the potential role of HBB haplotypes to predict beta-thalassemia in the Malaysian population. A total of 543 archived samples were selected for this study. Five tagging SNPs in the beta-globin gene (HBB; NG_000007.3) were analyzed for SNP-based and haplotype association using SHEsis online software. Single-SNP-based association analysis showed three SNPs have a statistically significant association with beta-thalassemia. When Bonferroni correction was applied, four SNPs were found statistically significant with beta-thalassemia; IVS2-74T>G (p adj = 0.047), IVS2-16G>C (p adj = 0.017), IVS2-666C>T (p adj = 0.017) and 3’UTR + 314G>A (p adj = 0.002). However, 3'UTR + 233G>C did not yield a significant association with p adj value = 0.076. Further investigation using combined five SNPs for haplotype association analysis revealed three susceptible haplotypes with significant p values of which, haplotypes 1-2-2-1-1 (p = 6.49 × 10−7, OR = 10.371 [3.345–32.148]), 1-2-1-1-1 (p = 0.009, OR = 1.423 [1.095–1.850] and 1-1-1-1-1 (p = 1.39 × 10−4, OR = 10.221 [2.345–44.555]). Three haplotypes showed protective effect with significant p value of which, 2-2-1-1-1 (p = 0.006, OR = 0.668 [0.500–0.893]), 1-1-2-2-1 (p = 0.013, OR = 0.357 [0.153–0.830]) and 1-1-2-1-1 (p = 0.033, OR = 0.745 [0.567–0.977]). This study has identified the potential use of intragenic polymorphic markers in the HBB gene, which were significantly associated with beta-thalassemia. Combining these five SNPs defined a new haplotype model for beta-thalassemia and further evaluation for predicting severity in beta-thalassemia. |
| format |
article |
| author |
Nur-Aisyah Aziz Wan-Rohani Wan Taib Nur-Khairunnisa Kharolazaman Imilia Ismail Hamid Ali Nagi Al-Jamal Nadiah Wan-Arfah Wan Abdul Jamil Ezalia Esa Hishamshah Ibrahim |
| author_facet |
Nur-Aisyah Aziz Wan-Rohani Wan Taib Nur-Khairunnisa Kharolazaman Imilia Ismail Hamid Ali Nagi Al-Jamal Nadiah Wan-Arfah Wan Abdul Jamil Ezalia Esa Hishamshah Ibrahim |
| author_sort |
Nur-Aisyah Aziz |
| title |
Evidence of new intragenic HBB haplotypes model for the prediction of beta-thalassemia in the Malaysian population |
| title_short |
Evidence of new intragenic HBB haplotypes model for the prediction of beta-thalassemia in the Malaysian population |
| title_full |
Evidence of new intragenic HBB haplotypes model for the prediction of beta-thalassemia in the Malaysian population |
| title_fullStr |
Evidence of new intragenic HBB haplotypes model for the prediction of beta-thalassemia in the Malaysian population |
| title_full_unstemmed |
Evidence of new intragenic HBB haplotypes model for the prediction of beta-thalassemia in the Malaysian population |
| title_sort |
evidence of new intragenic hbb haplotypes model for the prediction of beta-thalassemia in the malaysian population |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/b6f83b202f7944819ba8a21e16708e7e |
| work_keys_str_mv |
AT nuraisyahaziz evidenceofnewintragenichbbhaplotypesmodelforthepredictionofbetathalassemiainthemalaysianpopulation AT wanrohaniwantaib evidenceofnewintragenichbbhaplotypesmodelforthepredictionofbetathalassemiainthemalaysianpopulation AT nurkhairunnisakharolazaman evidenceofnewintragenichbbhaplotypesmodelforthepredictionofbetathalassemiainthemalaysianpopulation AT imiliaismail evidenceofnewintragenichbbhaplotypesmodelforthepredictionofbetathalassemiainthemalaysianpopulation AT hamidalinagialjamal evidenceofnewintragenichbbhaplotypesmodelforthepredictionofbetathalassemiainthemalaysianpopulation AT nadiahwanarfahwanabduljamil evidenceofnewintragenichbbhaplotypesmodelforthepredictionofbetathalassemiainthemalaysianpopulation AT ezaliaesa evidenceofnewintragenichbbhaplotypesmodelforthepredictionofbetathalassemiainthemalaysianpopulation AT hishamshahibrahim evidenceofnewintragenichbbhaplotypesmodelforthepredictionofbetathalassemiainthemalaysianpopulation |
| _version_ |
1718381519324577792 |