Alpha-1-antitrypsin deficiency in the Cape Verde islands (Northwest Africa): High prevalence in a sub-Saharan population

Abstract

Alpha-1-antitrypsin (AAT) deficiency results from mutations on the Protease Inhibitor (PI) locus located in chromosome 14 and has been associated with pulmonary early-onset emphysema and chronic obstructive pulmonary disease (COPD). African populations show a lower prevalence of AAT deficiency compared to Europeans. Two hundred and two (202) unrelated samples from the Cape Verde archipelago (Northwest Africa) were genotyped for the two most common AAT deficiency alleles, PI*S and PI*Z, using PCR - Mediated Site-Directed Mutagenesis. PI*S mutation in Cape Verde (3.2%) presents one of the highest frequencies in sub-Saharans, similar to South Africa (3.3%) but lower than Angolans (18.8%), Namibians (14.7%), Nigerians (6.4%) and Botswains (4.5%). The PI*Z mutation shows lower values (0.2%) than other sub-Saharan populations, namely Somalia (1.15%), Mali (0.98%)or Nigeria (0.36%). However, many other sub-Saharan populations, like Botswana, Congo, Cameroon, Angola, Gambia, South Africa, Mozambique and Namibia, lack the PI*Z mutation. The frequency of all the AAT deficiency genotypes in the Cape Verde archipelago (PI*ZZ, PI*SS, and PI*SZ) was estimated to be one of the highest in sub-Saharans (15 per 1000), only lower than Angola (54 per 1000) and Namibia (22 per 1000). The results obtained show a high prevalence of the AAT deficiency in Cape Verdeans when compared to other sub-Saharans a condition that can be explained by a heavy European genetic influence, characteristic of that population.

Genetic Epidemiology of Alpha-1 Antitrypsin Deficiency in Macaronesia

“…In 2009, Spínola and collaborators published a study on 202 unrelated adults Cape Verdeans, genotyped with an allele-specific PCR technique for PI*S and PI*Z, finding a gene frequency of 35/1,000 for PI *S and 2/1,000 for PI*Z [22] (Table 3), both much lower than those of La Palma and Madeira. Cape Verde is an archipelago located in the North Atlantic Ocean, west of Senegal.…”

“…A bibliographic search was carried out in MEDLINE, Embase (through Ovid), and Google Scholar, until December 2023, looking for studies on prevalence of AATD in the general population and in screening of people clinically suspected of being affected by AATD in Macaronesia, selecting studies published in journals reviewed by peers in order to create a database with reliable results. With the keywords "Alpha-1 antitrypsin deficiency" and the name of each archipelago, in English, and some articles cited in the bibliography of those selected, 16 articles were compiled: 2 on Madeira [7,8], 13 on the Canary Islands [9][10][11][12][13][14][15][16][17][18][19][20][21], and 1 on Cape Verde [22]. None was found about the Azores.…”

“…To select those relating to the prevalence of AATD in the general population, the following criteria were applied: (1) samples made up of healthy unrelated people; (2) minimum sample size of 200 subjects (400 alleles); (3) phenotypes or genotypes characterized with reliable techniques, including isoelectrofocusing, real-time allele-specific PCR, PCR-Luminex [23,24], and gene sequencing. With this methodology, three studies carried out in the general population of Madeira [7], La Palma (Canary Islands) [11], and Cape Verde [22] were selected. In addition, three screening studies aimed at detecting AATD in respiratory patients with COPD or asthma, two carried out in La Palma [11] and one in Gran Canaria [17] were selected.…”

Advances in managing COPD related to α1‐antitrypsin deficiency: An under‐recognized genetic disorder

“…While PI*Z and PI*S alleles are particularly prevalent in the north and south of Europe, respectively, deficiency alleles have been detected across diverse populations worldwide . By combining data from epidemiological studies, in 2012 de Serres and Blanco estimated the prevalence of AAT alleles across 10 geographic regions worldwide, encompassing 97 countries and 5.26 billion people.…”

Alpha-1 Antitrypsin Deficiency in Iranian Patients with Chronic Obstructive Pulmonary Disease

“…Deficiency alleles other than PI*S and PI*Z have very rarely been reported (1). AAT deficiency is associated with severe pulmonary emphysema and chronic obstructive pulmonary disease (COPD) (3). The prevalence of AAT in COPD patients varies from one country to another (4).…”