Hb S [ß6(A3)Glu→Val, GAG>GTG] in Mexican Mestizos: frequency and analysis of the 5' ß-globin haplotype.

Between 1978 and 2009, we studied 1,863 Mexican Mestizo patients with clinical data compatible with a hemoglobinopathy. Of these patients, 382 had some hemoglobin (Hb) abnormality (20.5%), 128 had a sickle cell hemoglobinopathy, representing a general frequency of 6.9%, which is similar to the percentage observed in previous studies on Mexican Mestizos. We analyzed the 5' ß-globin haplotype (5'Hp) in 79 unrelated ß(S) chromosomes (26 ß(S)/ß(S), 14 ß(S)/ß(Thal), nine ß(S)/ß(A) and four ß(S)/ß(D)), and four haplotypes were observed: 72.2% CAR 24.1% Benin, 2.5% Senegal and 1.2% Cameroon; the last two are reported for first time in Mexico. In some Latin American populations such as Brazil, the Bantu haplotype predominates, while in others such as Jamaica, the Benin haplotype is the most frequent, showing heterogeneity of African genes as a consequence of different regions involved in the slave trade.

Diversity of the 5' beta-globin haplotype of four beta-thalassemia mutations in the Mexican population.

beta-Globin haplotypes have been used to investigate the origin and spread of beta-globin mutations such as Hb S [beta 6(A3)Glu-->Val, GAG>GTG], Hb E [beta 26(B8)Glu-->Lys, GAG>AAG], and beta-thalassemia (beta-thal). Molecular analyses revealed the presence of 17 beta-thal mutations in the Mexican population; the most frequent of these are the nonsense codon 39 (C>T), IVS-I-1 (G>A), IVS-I-110 (G>A), and -28 (A>C). To improve our knowledge about their origin, we analyzed the 5' haplotypes by restriction fragment length polymorphism. The codon 39 mutation (n = 17) was observed with five 5' haplotypes: 1 (59%), 2 (23%), and 4, 6, and 9 (6% each). The IVS-I-1 mutation (n = 15) was found with five 5' haplotypes: 1 (73.6%), 2, 3, 5, and 11 (6.6% each), whereas the IVS-I-110 (n = 9) and -28 mutations (n = 1) were only associated with haplotype 1. In the population studied, the codon 39 and IVS-I-1 mutations show a multicentric origin, whereas the IVS-I-110 and -28 mutations have an apparent single origin. Further investigation is required for the analysis of the polymorphisms surrounding the beta-globin gene.