Screening for β-thalassemia trait (BTT) relies on measuring hemoglobin (Hb) A2. Since multiple factors can affect HbA2 levels, the screening can become unreliable. In 1356 healthy Arabs enrolled into a federally funded premarital BTT screening program, the effects of iron deficiency (ID), -thalassemia trait, gender, smoking, and tribalism on HbA2 were studied. The complete blood count and hemoglobin fractions were determined on the entire cohort; serum ferritin (<15？μg/L) in 391 subjects was used to determine ID. BTT was present in 29 (2.1%) subjects (HbA2 > 3.5%). Among 77(20.3%) subjects with ID, the mean HbA2 ( %) was 0.2% lower than in subjects without iron deficiency ( %, ). In 65 (38%)/172 subjects with phenotypic -thalassemia trait, the mean HbA2 ( %) was 0.13% lower than in subjects without -thalassemia trait, . The mean HbA2 did not differ between males and females, smokers and nonsmokers, and between the tribes. Thus, 35 (2.6%) subjects with HbA2 between 3.2 and 3.5% were at a risk of false negative diagnosis of BTT. Since iron deficiency and -thalassemia are both common and both lower HbA2, modifications in screening recommendations for BTT are proposed. 1. Introduction Screening for β-thalassemia trait (BTT) depends on measuring hemoglobin (Hb) A2 accurately. However, since many factors like iron deficiency, α-thalassemia, β-gene mutations, gender, and smoking may affect HbA2 levels, the screening of BTT can be compromised [1–5]. The United Arab Emirates (UAE) is a multiethnic country with a BTT screening program because of a heavy burden of β-thalassemia disease. Consanguinity is common and marriages in the native population are arranged within the same tribe, which restricts gene flow and produces a heterogeneous distribution of BTT [6, 7]. As a preventive measure, mandatory federal premarital screening has been instituted throughout the UAE. In this population, though iron deficiency is common, iron stores are not routinely evaluated during the screening for BTT. In addition, α-thalassemia mutations are also frequent; this is important for BTT screening since their coinheritance with β-thalassemia mutations may lower the level of HbA2. Furthermore, α-thalassemia alters MCV and MCH, which adds to the risk of a missed diagnosis of BTT [2, 8]. In the UAE, 44 different β-thalassemia mutations have been reported though their phenotype, and the prevalence of silent mutations have not been systematically investigated [9–13]. Moreover, in this population the differences in lifestyle between genders might affect HbA2; for example, smoking is
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