Licínio Manco, Afonso Marques Morais, Sara Miguel Almeida, Inês Salgado, Luís Relvas, Celdidy Monteiro, Guilherme Queiroz, Celeste Bento
{"title":"<s:1> o tom<s:1> e Príncipe HbAA和HbAS女性中HbF的遗传修饰因子：BCL11A、MYB、HBG2和BGLT3常见遗传变异的关联研究","authors":"Licínio Manco, Afonso Marques Morais, Sara Miguel Almeida, Inês Salgado, Luís Relvas, Celdidy Monteiro, Guilherme Queiroz, Celeste Bento","doi":"10.31083/FBS38388","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>While an increase in fetal hemoglobin (HbF) has no consequences in healthy adults, clinical benefits can be promoted in sickle cell disease (SCD) and β-thalassemia patients. Single-nucleotide polymorphisms (SNPs) in three genomic regions: the <i>HBB</i> gene cluster, the <i>BCL11A</i> gene, and the <i>HBS1L-MYB</i> (<i>HMIP</i>) intergenic region, have been associated with HbF regulation. Therefore, the present study aimed to examine the potential association of SNPs in <i>BCL11A</i> (rs11886868 and rs1427407), <i>HMIP</i> (rs66650371 and rs4895441), <i>HBG2</i> (rs7482144), and <i>BGLT3</i> (rs7924684) with HbF levels in an adult population sample from São Tomé e Príncipe (Central Africa).</p><p><strong>Methods: </strong>A total of 145 women aged 18 to 49 years were involved in this study, comprising 98 women with the normal hemoglobin (Hb) genotype (HbAA) and 47 with sickle cell trait (HbAS). From the HbAA individuals, we selected a control group of 60 subjects with normal HbF levels, ranging from 0.2% to 1.4% (mean: 0.75%), and a case group of 38 subjects with elevated HbF levels, ranging from 1.8% to 3.7% (mean: 2.35%). In the group of HbAS individuals, the HbF levels ranged from 0.4% to 3.7% (mean: 1.56%). SNP genotyping was conducted using standard molecular methods.</p><p><strong>Results: </strong>Logistic regression, in the additive model, revealed significant associations with increased levels of HbF for the minor alleles of the two <i>BCL11A</i> SNPs, rs11886868 [C] and rs1427407 [T], in HbAA women (<i>p</i> = 0.00018 and <i>p</i> = 0.00076, respectively). When comparisons of HbF levels were conducted among genotypes in the HbAA women, significant differences were observed for <i>BCL11A</i> SNPs rs11886868 and rs1427407, as well as for the <i>HBG2</i> rs7482144 and <i>BGLT3</i> rs7924684 variants. We found no association between HbF levels and the two <i>HMIP</i> variants rs66650371 and rs4895441 in the HbAA women. Among the HbAS women, no statistically significant associations were observed between the six analyzed polymorphisms and HbF levels (<i>p ></i> 0.05).</p><p><strong>Conclusions: </strong>We successfully replicated the association between the two well-known <i>BCL11A</i> SNPs, rs11886868 and rs1427407, with HbF levels in women with the normal HbAA genotype from São Tomé e Príncipe. Other signals of association with HbF levels were identified for the SNPs <i>HBG2</i> (rs7482144) and <i>BGLT3</i> (rs7924684).</p>","PeriodicalId":73070,"journal":{"name":"Frontiers in bioscience (Scholar edition)","volume":"17 2","pages":"38388"},"PeriodicalIF":0.0000,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genetic Modifiers of HbF in HbAA and HbAS Women From São Tomé e Príncipe: An Association Study of Common Genetic Variants in <i>BCL11A</i>, <i>MYB</i>, <i>HBG2</i>, and <i>BGLT3</i>.\",\"authors\":\"Licínio Manco, Afonso Marques Morais, Sara Miguel Almeida, Inês Salgado, Luís Relvas, Celdidy Monteiro, Guilherme Queiroz, Celeste Bento\",\"doi\":\"10.31083/FBS38388\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>While an increase in fetal hemoglobin (HbF) has no consequences in healthy adults, clinical benefits can be promoted in sickle cell disease (SCD) and β-thalassemia patients. Single-nucleotide polymorphisms (SNPs) in three genomic regions: the <i>HBB</i> gene cluster, the <i>BCL11A</i> gene, and the <i>HBS1L-MYB</i> (<i>HMIP</i>) intergenic region, have been associated with HbF regulation. Therefore, the present study aimed to examine the potential association of SNPs in <i>BCL11A</i> (rs11886868 and rs1427407), <i>HMIP</i> (rs66650371 and rs4895441), <i>HBG2</i> (rs7482144), and <i>BGLT3</i> (rs7924684) with HbF levels in an adult population sample from São Tomé e Príncipe (Central Africa).</p><p><strong>Methods: </strong>A total of 145 women aged 18 to 49 years were involved in this study, comprising 98 women with the normal hemoglobin (Hb) genotype (HbAA) and 47 with sickle cell trait (HbAS). From the HbAA individuals, we selected a control group of 60 subjects with normal HbF levels, ranging from 0.2% to 1.4% (mean: 0.75%), and a case group of 38 subjects with elevated HbF levels, ranging from 1.8% to 3.7% (mean: 2.35%). In the group of HbAS individuals, the HbF levels ranged from 0.4% to 3.7% (mean: 1.56%). SNP genotyping was conducted using standard molecular methods.</p><p><strong>Results: </strong>Logistic regression, in the additive model, revealed significant associations with increased levels of HbF for the minor alleles of the two <i>BCL11A</i> SNPs, rs11886868 [C] and rs1427407 [T], in HbAA women (<i>p</i> = 0.00018 and <i>p</i> = 0.00076, respectively). When comparisons of HbF levels were conducted among genotypes in the HbAA women, significant differences were observed for <i>BCL11A</i> SNPs rs11886868 and rs1427407, as well as for the <i>HBG2</i> rs7482144 and <i>BGLT3</i> rs7924684 variants. We found no association between HbF levels and the two <i>HMIP</i> variants rs66650371 and rs4895441 in the HbAA women. Among the HbAS women, no statistically significant associations were observed between the six analyzed polymorphisms and HbF levels (<i>p ></i> 0.05).</p><p><strong>Conclusions: </strong>We successfully replicated the association between the two well-known <i>BCL11A</i> SNPs, rs11886868 and rs1427407, with HbF levels in women with the normal HbAA genotype from São Tomé e Príncipe. Other signals of association with HbF levels were identified for the SNPs <i>HBG2</i> (rs7482144) and <i>BGLT3</i> (rs7924684).</p>\",\"PeriodicalId\":73070,\"journal\":{\"name\":\"Frontiers in bioscience (Scholar edition)\",\"volume\":\"17 2\",\"pages\":\"38388\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-06-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in bioscience (Scholar edition)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.31083/FBS38388\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in bioscience (Scholar edition)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.31083/FBS38388","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
背景：虽然胎儿血红蛋白（HbF）的增加在健康成人中没有后果，但在镰状细胞病（SCD）和β-地中海贫血患者中可以促进临床益处。三个基因组区域的单核苷酸多态性（snp）： HBB基因簇、BCL11A基因和HBS1L-MYB （HMIP）基因间区域与HbF调控有关。因此，本研究旨在研究 o tom e Príncipe（中非）成人人群样本中BCL11A （rs11886868和rs1427407）、HMIP （rs66650371和rs4895441）、HBG2 （rs7482144）和BGLT3 (rs7924684) snp与HbF水平的潜在关联。方法：145名年龄在18 ~ 49岁的女性参与了这项研究，其中98名女性具有正常血红蛋白（Hb）基因型（HbAA）， 47名女性具有镰状细胞特征（HbAS）。从HbAA个体中，我们选择了60名HbF水平正常的受试者作为对照组，范围从0.2%到1.4%（平均：0.75%），以及38名HbF水平升高的受试者，范围从1.8%到3.7%（平均：2.35%）。在HbAS个体组中，HbF水平从0.4%到3.7%不等（平均：1.56%）。采用标准分子方法进行SNP基因分型。结果：在加性模型中，Logistic回归显示HbAA女性中两个BCL11A snp的次要等位基因rs11886868 [C]和rs1427407 [T]的HbF水平升高具有显著相关性（p = 0.00018和p = 0.00076）。当比较HbAA女性中不同基因型的HbF水平时，发现BCL11A snp rs11886868和rs1427407以及HBG2 rs7482144和BGLT3 rs7924684变异存在显著差异。在HbAA女性中，我们发现HbF水平与两种HMIP变体rs66650371和rs4895441之间没有关联。在HbAS女性中，6种分析的多态性与HbF水平之间无统计学意义的关联（p < 0.05）。结论：我们成功地复制了两个著名的BCL11A snp rs11886868和rs1427407与 o tom e Príncipe正常HbAA基因型女性HbF水平之间的关联。其他与HbF水平相关的信号被鉴定为snp HBG2 （rs7482144）和BGLT3 （rs7924684）。
Genetic Modifiers of HbF in HbAA and HbAS Women From São Tomé e Príncipe: An Association Study of Common Genetic Variants in BCL11A, MYB, HBG2, and BGLT3.
Background: While an increase in fetal hemoglobin (HbF) has no consequences in healthy adults, clinical benefits can be promoted in sickle cell disease (SCD) and β-thalassemia patients. Single-nucleotide polymorphisms (SNPs) in three genomic regions: the HBB gene cluster, the BCL11A gene, and the HBS1L-MYB (HMIP) intergenic region, have been associated with HbF regulation. Therefore, the present study aimed to examine the potential association of SNPs in BCL11A (rs11886868 and rs1427407), HMIP (rs66650371 and rs4895441), HBG2 (rs7482144), and BGLT3 (rs7924684) with HbF levels in an adult population sample from São Tomé e Príncipe (Central Africa).
Methods: A total of 145 women aged 18 to 49 years were involved in this study, comprising 98 women with the normal hemoglobin (Hb) genotype (HbAA) and 47 with sickle cell trait (HbAS). From the HbAA individuals, we selected a control group of 60 subjects with normal HbF levels, ranging from 0.2% to 1.4% (mean: 0.75%), and a case group of 38 subjects with elevated HbF levels, ranging from 1.8% to 3.7% (mean: 2.35%). In the group of HbAS individuals, the HbF levels ranged from 0.4% to 3.7% (mean: 1.56%). SNP genotyping was conducted using standard molecular methods.
Results: Logistic regression, in the additive model, revealed significant associations with increased levels of HbF for the minor alleles of the two BCL11A SNPs, rs11886868 [C] and rs1427407 [T], in HbAA women (p = 0.00018 and p = 0.00076, respectively). When comparisons of HbF levels were conducted among genotypes in the HbAA women, significant differences were observed for BCL11A SNPs rs11886868 and rs1427407, as well as for the HBG2 rs7482144 and BGLT3 rs7924684 variants. We found no association between HbF levels and the two HMIP variants rs66650371 and rs4895441 in the HbAA women. Among the HbAS women, no statistically significant associations were observed between the six analyzed polymorphisms and HbF levels (p > 0.05).
Conclusions: We successfully replicated the association between the two well-known BCL11A SNPs, rs11886868 and rs1427407, with HbF levels in women with the normal HbAA genotype from São Tomé e Príncipe. Other signals of association with HbF levels were identified for the SNPs HBG2 (rs7482144) and BGLT3 (rs7924684).
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