Sickle cell disorder, β-globin gene cluster haplotypes and α-thalassemia in neonates and adults from Guadeloupe

Abstract

We have studied haplotype of ␤ S chromosome and ␣-globin gene status in 534 patients (255 adults and 279 children of whom 159 neonates) from Guadeloupe with various sickle cell-related conditions, namely SS (n = 298), SC (n = 170), S-␤-thal (n = 56), and other rare forms (n = 10). Haplotype data on ␤ S chromosomes confirm our previous observation that Benin type is the most prevalent (75%) ␤ S chromosome in Guadeloupe, in disagreement with the historical records. Comparison of the frequency of distribution of various ␤ S haplotypes between neonates and adults on the one hand and between SS and SC cases on the other shows that the current ␤ S haplotype distribution in this island is not distorted by haplotype-related differential survival. We also show that the frequency of ␣-thalassemia (−3.7 kb) in Guadeloupe is one of the highest recorded in this region involved in Atlantic slave trade and also failed to reveal any age-dependent increase in frequency. We conclude that the African component of Guadeloupe is distinct from that of Brazil and Cuba but is close to that of Jamaica. Am.

Genetic polymorphism of the mannose-binding protein gene in children with sickle cell disease: identification of three new variant alleles and relationship to infections

“…This is best illustrated by the fact that 67% of these children are homozygotes for a given s -globin haplotype even though the relative allelic representation of the Benin, Bantu (CAR), and Senegal haplotypes among the overall population was 1:1:0.7, ie a clear bias in a Hardy-Weinberg distribution (results not shown). This is in contrast to the distribution of the s -globin haplotype observed in our patients from the West Indies and in a series from Jamaica 1,22 or North America 23 which clearly indicates the genetic admixture of these populations. Thus our data can be reasonably interpreted in epidemiological terms concerning the distribution of MBP variants in African populations.…”

Characterization of β-globin haplotypes using blood spots from a population-based cohort of newborns with homozygous HbS

“…34 To our knowledge, the estimated frequency of ␤-globin haplotypes among chromosomes from Hispanics is the only available description for Hispanics born in the United States. Compared with available estimates of Central/South American and Caribbean ␤-globin haplotype diversity, the distribution of haplotypes in this Hispanic population is similar to that described for Venezuela 35 and Cuba, 36 but different from that described for Jamaica, 6,7,34 Guadeloupe, 37 Colombia, 38 and Brazil. 39 As expected, the black population reported here had more distinct haplotypes and haplotype combinations than the Hispanic population.…”

“…Although the data from that study have not been replicated, 35,37,38 investigators should note that the prevalence of genotypes determined from blood spots could be limited to a newborn population, depending on the disorder being studied. A second potential problem related to the use of blood spots is that each spot represents a diploid genome.…”

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

“…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].…”

“…The effect of a-thalassemia on hematological and clinical parameters was analyzed on the whole group as well as on groups stratified according to their UGT1A1 genotype [4,8]. Differences in hematological data between patient groups were assessed using Kruskal-Wallis tests, and cholelithiasis prevalence was assessed by Pearson's statistic.…”