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

Abstract

Communicated by Jürgen HorstWe have tabulated the 77 currently known mutations of the familiar human blood protein, serum albumin (ALB). A total of 65 mutations result in bisalbuminemia. Physiological and structural effects of these mutations are included where observed. Most of the changes are benign. The majority of them were detected upon clinical electrophoretic studies, as a result of a point mutation of a charged amino acid residue. Three were discovered by their strong binding of thyroxine or triiodothyronine. A total of 12 of the tabulated mutations result in analbuminemia, defined as a serum albumin concentration of o1 g/L. These were generally detected upon finding a low albumin concentration in patients with mild edema, and involve either splicing errors negating translation or premature stop codons producing truncated albumin molecules. A total of nine mutations, five of those with analbuminemia and four resulting in variants modified near the C-terminal end, cause frameshifts. Allotypes from three of the point mutations become N-glycosylated and one C-terminal frameshift mutation shows O-glycosylation. Hum Mutat 29(8), [1007][1008][1009][1010][1011][1012][1013][1014][1015][1016] 2008.

Sulfenic acid—A key intermediate in albumin thiol oxidation

“…At least 77 mutations have been identified in the albumin gene [24]. In addition, there are 43 registered cases of analbuminemia that leads to low blood pressure, edema, fatigue, hypercholesterolemia and lipodystrophy (http://www.albumin.org/).…”

Human serum albumin: From bench to bedside

“…SA was named a century and half ago (Denis, 1859) and deeply investigated over the last century (Peters, 1996). In 1932, HSA was separated from plasma proteins (Race, 1932); in 1934, HSA was crystallized (Hewitt, 1936); in 1939, the neutral-to-acid (i.e., N-to-F) conformational transition was detected (Luetscher, 1947); in 1940, HSA was purified for intravenous use as a blood substitute (Cohn, 1941); in 1954, the first two cases of analbuminemia were reported (Bennhold et al, 1954); in 1960, the HSA ''domain'' structure was proposed (Foster, 1960); in 1975, the primary structure of HSA was deduced (Meloun et al, 1975), and the characterization of specific drug binding sites started (Sudlow et al, 1975); in 1979, the HSA gene was isolated (Sargent et al, 1979); in 1981, the nucleotide sequence of HSA cDNA was reported (Lawn et al, 1981); in 1986, the complete gene sequence of HSA was determined (Minghetti et al, 1986), and the expression, the cleavage, and the secretion of HSA from cultured yeast Saccharomyces cerevisiae was reported (Hinchcliffe and Kenney, 1986); starting from 1989, many HSA mutations were localized (Peters, 1996;Minchiotti et al, 2008;Otagiri and Chuang, 2009); in 1992, the ''heart-shaped'' three-dimensional structure of HSA was determined (He and Carter, 1992); in 1995, the ferrous tetraphenylporphirinatoiron (FeP(II)) was incorporated in HSA to obtain a red blood cell substitute (Komatsu et al, 1995); in 1999, the role of HSA in heme-Fe scavenging was highlighted (Miller and Shaklai, 1999), and human serum heme-albumin (HSA-heme) was engineered to become a O 2 carrier (Carter et al, 1999;Komatsu et al, 2004a); and starting from 2001, the detoxifying role of HSA-heme-Fe towards reactive nitrogen species (RNS) and reactive oxygen species (ROS) was underlined (Monzani et al, 2001;Ascenzi et al, 2009a).…”

Effects of human serum albumin complexed with free fatty acids on cell viability and insulin secretion in the hamster pancreatic β-cell line HIT-T15

“…There have been very few studies that have attempted to study FFA binding to genetic variants of HSA. Although a few noted increased FFA binding (Minchiotti et al, 2008), majority of the mutations had none or less effect, especially those on the surface of the protein (Otagiri and Chuang, 2009). Therefore, while the existence of other genetic HSA variants in the populace remains to be screened or unknown, our study presents a possible mechanism on what alterations on HSA has on FFA binding since we carried out amino acid substitutions in key FFAbinding pockets of HSA.…”