A Population-Oriented Genetic Scoring System to Predict Phenotype: A Pathway to Personalized Medicine in Iraqis With β-Thalassemia

• Published in: Hemoglobin 2024-03, Vol.48 (2), p.94-100
• Main Authors: Al-Allawi, Nasir, Atroshi, Sulav D, Sadullah, Regir K, Eissa, Adil Abozaid, Kriegshäuser, Gernot, Al-Zebari, Shaima, Qadir, Shatha, Khalil, Dilan, Oberkanins, Christian
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Alleles; alpha-Thalassemia - diagnosis; alpha-Thalassemia - genetics; beta-Thalassemia - diagnosis; beta-Thalassemia - genetics; Child; Child, Preschool; Female; Genotype; Humans; Iraq; Male; Phenotype; Polymorphism, Single Nucleotide; Precision Medicine; Repressor Proteins; Young Adult
• ISSN: 0363-0269; 1532-432X
• DOI: 10.1080/03630269.2024.2319733

To assess the roles of genetic modifiers in Iraqi β-thalassemia patients, and determine whether a genotype-based scoring system could be used to predict phenotype, a total of 224 Iraqi patients with molecularly characterized homozygous or compound heterozygous β-thalassemia were further investigated for α-thalassemia deletions as well as five polymorphisms namely: rs7482144 C > T at , rs1427407 G > T and rs10189857 A > G at and rs28384513 A > C and rs9399137 T > C at The enrolled patients had a median age of 14 years, with 96 males and 128 females. They included 144 thalassemia major, and 80 thalassemia intermedia patients. Multivariate logistic regression analysis revealed that a model including sex and four of these genetic modifiers, namely: β alleles, rs7482144, α-thalassemia deletions, and rs1427407 could significantly predict phenotype (major versus intermedia) with an overall accuracy of 83.9%. Furthermore, a log odds genetic score based on these significant predictors had a highly significant area under curve of 0.917 (95% CI 0.882-0.953). This study underscores the notion that genetic scoring systems should be tailored to populations in question, since genetic modifiers (and/or their relative weight) vary between populations. The population-oriented genetic scoring system created by the current study to predict β-thalassemia phenotype among Iraqis may pave the way to personalized medicine in this patient's group.