Albumin genetic variability in South America: Population distribution and molecular studies

Abstract

A total of 5,020 individuals living in two southern Brazilian states were screened in relation to albumin types; two variants were found, in Passo Fundo (Nagasaki 2) and Vera Cruz (Tradate 2). Another variant, detected in the northeast, was identified as Porto Alegre 2, which also occurs in other places in Brazil, as well as in India, Pakistan, and Turkey. The results were integrated with those obtained in other studies in South America, yielding a total of 16,941 Amerindians and 23,839 non-Indian subjects. Molecular and physiological studies performed in some of the variants suggested clues to explain the restricted distribution of albumin Yanomama 2 and the widespread occurrence of albumin Maku. Am. J. Hum. Biol. 11: 359-366, 1999. © 1999 Human serum albumin, the most abundant protein in blood plasma, is physiologically important due to its unique ability of reversibly binding an extensive series of endogenous and exogenous compounds. Structurally, it is a nonglycoprotein composed of a single polypeptide chain subdivided in three homologous domains, which total 585 amino acids. To date, more than 50 genetic variants of albumin have been characterized at the protein and/or DNA level. The molecular distribution of these changes is clearly nonrandom, with clusters at the propeptide, N-terminus, and C-terminal regions of subdomains II B and III B. Moreover, population prevalences of these variants also present several interesting features. They are rare in most ethnic groups, but show some polymorphic variants especially in Amerindians (see Madison et al., 1994;Nielsen et al., 1997).The present report presents: a) a detailed review of the population distribution of albumin variants in South America, including new data in 5,020 individuals; b) a description of the molecular changes in three Brazilian variants; and c) a review of the physiological studies performed in four of these types, trying to integrate all of the results in a unified manner.

Mutations and polymorphisms of the gene of the major human blood protein, serum albumin

“…The prevalence of albumin mutants is generally low, 0.0016 to 0.006 in several large studies [Carlson et al, 1992;Neel et al, 1988]. The variant with the widest geographical distribution is reported to be Albumin Coari-1 (p.Glu382Lys), found broadly in Brazil and in India, the United Kingdom, and Canada [Franco et al, 1999]. Albumin Oliphant, or B, (p.Glu594Lys) is the form most often reported in Caucasians in India, Japan, Cambodia, and six or more European nationalities [Carlson et al, 1992].…”

“…Albumin Naskapi (p.Lys396Glu) has a prevalence of 0.138 in Indian tribes of Labrador and of 0.022 in Alberta (Canada), and has been found in Turkey and the Punjab region of India [Takahashi et al, 1987b]. It mixes with Albumin Mexico (p.Asp574Gly) in Apaches of the U.S. desert southwest, and is found in some tribes in Brazil [Franco et al, 1999]. These variants have aided the interpretation of migrations of ancient Americans from Asia.…”

“…Albumin Yanomama-2 (p.Arg138Gly) is found at frequency 0.08 in this stone-age Brazilian tribe. Albumin Maku (p.Lys565Glu) and Albumin Makiritare-1 (mutant site not yet known) are other forms which are polymorphic among Brazilian tribes [Franco et al, 1999]. Porta et al [1992] showed dominance of Albumins Milano slow (p.Asp399His), Oliphant (p.Glu594Lys), Venezia (p.Gly596-ProfsX10), and Catania (p.Gln604LysfsX4) in isolated local areas of Italy.…”

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

“…At least in the case of itraconazole, this results in increased levels of unbound drug. 5 Structural variation in plasma proteins, such as is seen in the genetic variants of albumin, 6,7 may affect substrate binding, 8 but no relevant data are yet available as to whether this affects antifungal drugs.…”

Human Pharmacogenomic Variations and Their Implications for Antifungal Efficacy

“…Low serum albumin was associated with a modestly reduced concentration 1 h after dosing, possibly due to The albumin gene (ALB) is located on chromosome 4q11-q13. More than 50 functional SNPs in the albumin gene have been characterized (83,175). Functional SNPs that affect the affinity of albumin for drugs have been previously described (149,260).…”