Influence of α-Thalassemia on Cholelithiasis in SS Patients with Elevated Hb F

Abstract

Chronic hemolysis, with consequent hyperbilirubinemia, predisposes SS patients to pigment gallstones. The other factors which influence the development of stones in these patients have not been identified. We have carried out a combined prospective and retrospective study of SS patients in Kuwait and specifically investigated the influence of coexistent α-thal trait on the prevalence of gallstones. A total of 45 patients (30 males, 15 females) with ages ranging from 1 to 16 years (mean 7.2 ± 3.1) were studied. Most were either homozygotes for the Saudi Arabia/India haplotype (86.7%) or compound heterozygotes for this and the Benin haplotype (11.1%). They were screened for gallstones with ultrasonography. α-Globin genotypes were determined using a combination of PCR and allele-specific oligonucleotide hybridization techniques to identify the common α-thalassemia alleles in this population. Gallstones were detected in 7 (15.6%) patients (4 males, 3 females), whose mean age (10.5 ± 5.5 years) was significantly higher than that (6.8 ± 3.2 years) of those without stones (p < 0.01). The mean total Hb of the former (8.4 ± 0.8 g/dl) was also significantly (p < 0.05) lower than in the latter (9.5 ± 1.3 g/dl), while the difference in mean Hb F levels was not significant. None of the 4 α-thal homozygotes had gallstones while 2 of 13 heterozygotes and 5 of the 23 patients without coexistent α-thal had. The differences in these proportions are statistically significant (χ² = 20.4, p < 0.001). It therefore appears that coexistent α-thal decreases the chance of developing gallstones in Arab SS patients. This may be related to less hemolysis in such patients as shown by their higher mean Hb level.

UGT1A1 polymorphism outweighs the modest effect of deletional (−3.7 kb) α‐thalassemia on cholelithogenesis in sickle cell anemia

“…Unlike in SCA patients bearing the Arab-Indian b S haplotype [7] the protective effect of a-thalassemia for cholelithiasis is not observed in our SCA patients predominantly of Benin b S haplotype. Such a discrepancy between these SCA population groups could be related to significant reduction in hemolysis associated with higher mean HbF levels associated with the Arab-Indian b S haplotype and/or to much higher frequency of a-thalassemia than in our study population [9,10].…”

“…The promoter region of UGT1A1 gene contains a run of variable number of thymine-adenine repeats, (TA) n (n ¼ 5 to 8) with an inverse relationship between the size of this microsatellite and the promoter activity. We have previously shown that SCA patients fell into three risk groups according to their UGT1A1 genotype: group 1 [homozygous (TA) 6 /(TA) 6 and heterozygous with at least one (TA) 5 allele], group 2 [heterozygous (TA) 6 /(TA) 7 and (TA) 6 /(TA) 8 ], and group 3 [homozygous (TA) 7 /(TA) 7 and heterozygous (TA) 7 /(TA) 8 ], associated respectively with low, intermediate, and high mean unconjugated bilirubin levels and risk of cholelithiasis [4]. a-Thalassemia, frequently encountered in patients with SCA, is known to diminish the degree of hemolytic anemia [5,6] and has been associated with a lower occurrence of cholelithiasis in SCA patients bearing the Arab-Indian b S haplotype [7].…”

Early modification of sickle cell disease clinical course by UDP-glucuronosyltransferase 1A1 gene promoter polymorphism

“…It is known that the coinheritance of a-thalassaemia and SCD determinants reduces the mean corpuscular haemoglobin concentration of red blood cells, which tends to inhibit sickling. It was observed that the coexistence of athalassaemia decreases the chance of developing gallstones in Arab Indian haplotype SCD patients, which may be related to lower haemolysis, as suggested by their predisposition to present, in general, higher mean Hb levels (Haider et al 1998). In addition, Adekile et al (2005) observed that the b-globin haplotype and the coexisting athalassaemia did not have significant influence on serum bilirubin levels in Arab Indian haplotype SCD patients (Adekile et al 2005).…”

Avascular Necrosis of the Hip in Children with Sickle Cell Disease and High Hb F: Magnetic Resonance Imaging Findings and Influence of α-Thalassemia Trait

“…This protects them from many of the complications of the disease. In particular, they retain their splenic function and are less prone to severe bacterial infections [5, 6, 7, 8]. Brain infarcts, leg ulcers and hand-and-foot syndrome are all rare.…”