Hemoglobin (Hb) F has a modulatory effect on the clinical phenotype of β-thalassemia disease. High expression of Hb F in Hb E-related disorders has been noted, but the mechanism is not well understood. We have examined the association of a novel SNP rs11759328 on ARHGAP 18 gene and other known modulators with a variability of Hb F in Hb E-related disorders. Genotyping of SNP rs11759328 (G/A) was performed based on high-resolution melting analysis. The rs11759328 (A allele) was shown to be significantly associated with Hb F levels (p < 0.05) in heterozygous and homozygous Hb E. High levels of Hb F in both heterozygous and homozygous Hb E were also found to be associated with SNPs in the study of other modifying genes including KLF 1 mutation, rs7482144 (Gγ-XmnI), rs4895441, rs9399137 of (HBS1L-MYB), and rs4671393 (BCL11A). Multivariate analysis showed that KLF1 mutation and SNP rs11759328 (GA) (ARHGAP18) modulated Hb F expression in heterozygous Hb E. For homozygous Hb E, this was found to be related to five modifying factors, i.e., KLF1 mutation, rs4895441 (GG), rs9399137 (CC), rs4671393 (AA), and rs4671393 (GA). These results indicate that a novel SNP rs11759328 is a genetically modifying factor associated with increased Hb F in Hb E disorder.

中文翻译：

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Rho GTPase激活蛋白18基因上的新型SNP rs11759328与Hb F在血红蛋白E相关疾病中的表达有关。

血红蛋白（Hb）F对β地中海贫血疾病的临床表型具有调节作用。人们已经注意到Hb F相关疾病中Hb F的高表达，但是其机理尚不清楚。我们已经检查了关于ARHGAP 18基因的新型SNP rs11759328和其他已知的调节剂与Hb E相关疾病中Hb F的变异性。SNP rs11759328（G / A）的基因分型是基于高分辨率熔解分析进行的。rs11759328（等位基因）与杂合和纯合Hb E中的Hb F水平显着相关（p <0.05）。杂合和纯合Hb E中高水平的Hb F也被发现与SNP相关。研究其他修饰基因，包括KLF 1突变，rs7482144（Gγ-XmnI），rs4895441，rs9399137（HBS1L-MYB）和rs4671393（BCL11A）。多变量分析显示，KLF1突变和SNP rs11759328（GA）（ARHGAP18）调节了杂合Hb E中的Hb F表达。对于纯合Hb E，这与五个修饰因子有关，即KLF1突变，rs4895441（GG）， rs9399137（CC），rs4671393（AA）和rs4671393（GA）。这些结果表明，新的SNP rs11759328是与Hb E病患Hb F增加有关的遗传修饰因子。