Ethnic differences in the occurrence of the M1(ala²¹³) haplotype of alpha‐1‐antitrypsin in asthmatic and non‐asthmatic black and white South Africans

Abstract

An ethnic study of 175 individuals, comprising 65 black and 110 white South Africans, has shown a conclusive difference in the frequency of the M1(ala213) haplotype of α1‐antitrypsin (P < 0.00001). The M1(ala213) haplotype occurred more frequently in the black group. In the latter group, the frequency of the M1(ala213) haplotype was the same in both controls (0.55) and asthmatics (0.53). However, there was a significant difference in the frequencies (0.19 and 0.36) for the respective white groups (P < 0.01), the frequency of the M1(ala213) haplotype being much higher in the asthmatics. Apart from the above differences, there was also a difference in the elastase‐inhibitory capacities of the homozygote phenotypes M1(val213) vs M1(ala213) (P < 0.0001), this capacity being lower in the latter phenotype. We conclude that the occurrence of the M1(ala213) allele of α1‐antitrypsin differs in various ethnic groups and may play a role in asthma.

Polymorphisms in the SERPINA1 Gene and the Risk of Chronic Obstructive Pulmonary Disease in a Korean Population

“…The mechanism responsible for the association of the M2 allele with the risk of COPD remains to be elucidated. However, it has been observed that the M2 variant has lower elastase inhibitory capacity compared to the M1 Val variant 13,14 . Therefore, it is possible that individuals with the M2 variant have lower elastase inhibitory capacity, and are thus prone to develop COPD.…”

“…In the previous studies 7,8,26 , the AAT phenotype was only determined by isoelectric focusing of serum and the serum AAT levels without measuring functional activity of the AAT protein. Although the M2 variant does not affect serum AAT levels, it may alter the functional activity of the AAT protein 13,14 , and thus predispose to the development of COPD.…”

“…The M variants are characterized by normal plasma AAT levels and are thought to be unrelated to any disease 7,12 . However, Gaillard et al 13,14 reported that the M1 Ala and M2 alleles had a significantly lower elastase inhibitory capacity compared to the M1 Val allele. In addition, a number of studies have observed an increased prevalence of the M1 Ala and M2 allele in asthmatics [13][14][15] .…”

“…However, Gaillard et al 13,14 reported that the M1 Ala and M2 alleles had a significantly lower elastase inhibitory capacity compared to the M1 Val allele. In addition, a number of studies have observed an increased prevalence of the M1 Ala and M2 allele in asthmatics [13][14][15] . These results suggest that the M1 Ala and M2 alleles may play a role in the inflammatory reaction and/or the elastase-antielastase balance, which are important in the pathogenesis of COPD.…”

Origins and spreads of Alpha 1 antitrypsin variants in world human populations: a synthetic review

“…However, in the first genetic investigations of human populations authors have used classical genetic markers such as those of ABO blood groups, the PI system of alpha 1 antitrypsin, HLA Loci, Rhesus system and particularly those of immunoglobulin GM system known by its unparalleled ability, of a single system, to differentiate human populations (for review see Chaabani, 2002). variant is more present in sub-Saharan subjects than in Europeans (Gaillard et al, 1994;Hayes, 2003). The Indian populations of South America were characterized by the high presence of PIM3 allele.…”