Genetic and Clinical Characteristics of Thalassemia Trait and Construction of
LASSO
‐Based Model for Its Differentiating From Iron Deficiency Anemia in Northern China
Wen‐jie Yu, Feng‐qi Zhang, Jia‐feng Niu, Rui Ma, Yin‐ting Ma, Guang‐ping Li, Yan Long ABSTRACT
Background
Thalassemia trait (TT) and iron deficiency anemia (IDA) represent the most common causes of microcytic hypochromic anemia (MHA) and are challenging to differentiate in clinical settings. Data regarding the genetic and clinical characteristics of TT in Northern China remain insufficient, highlighting an urgent need for rapid and efficient diagnostic strategies for the regional population.
Methods
This retrospective study enrolled 482 TT and 640 IDA patients from Northern China. Twenty‐seven α‐ and β‐TT mutations were detected by multicolor probe melting curve analysis (MMCA) and further confirmed by Sanger sequencing. A LASSO regression model using routine hematological indices was constructed and further validated. The diagnostic efficacy was compared with other indices (Mentzer, Shine and Lal, and Green and King indices).
Results
A total of 482 cases with TT mutations were identified. β‐TT mutations were the most prevalent ( n = 261, 54.15%), followed by α‐TT mutations ( n = 209, 43.36%) and α+β complex TT mutations ( n = 12, 2.49%). Among which, eight α‐TT genotypes, eleven β‐TT genotypes, and eight α+β compound genotypes mutations were detected. For α‐TT, the predominant genotype was _α SEA /αα (77.0%), followed by _α 3.7 /αα (14.3%), α SEA /_α 3.7 (3.3%) and the rare HKαα (1.0%). The three most prevalent genotypes among β‐TT mutations were HBB:c.316_197C>T heterozygous ( het ) (35.2%), HBB:c.124_127delTTCT het (29.5%), and HBB:c.52A>T het (23.4%). α‐TT minor (33.82%) and β‐TT minor (53.94%) contributed the predominant phenotypes. The LASSO‐nomogram based on RBC, MCV, MCHC, and RDW‐SD achieved favorable discriminative performance (AUC = 0.94, sensitivity = 90.0%, specificity = 91.8%), showing superior diagnostic efficacy than other indices.
Conclusion
Our study revealed a distinct β‐TT‐dominant genotypic profile in Northern China and provided a simple, region‐adapted model as a potential tool for differentiating TT from IDA in clinical practice.