Carbon monoxide concentration in donated blood: relation to cigarette smoking and other sources.

BACKGROUND: Carbon monoxide (CO) is normally present in the human body due to endogenous production of CO. CO can also be inhaled by exposure to external sources such as cigarette smoke, car exhaust, and fire. The purpose of this study was to investigate CO concentrations in blood from 410 blood donors at the blood center in Umeå, Sweden. To further evaluate the effects of cigarette smoking on CO concentrations, the elimination time for CO was examined in six volunteer smokers after a smoked cigarette. STUDY DESIGN AND METHODS: Blood samples from whole blood donors were obtained during the blood center's routine operation. In connection with blood donations, demographic and behavioral data were collected from the donors. The CO concentration was determined using gas chromatography. RESULTS: The majority of blood donors had approximately the same CO concentration (mean, 84.5 micromol/L). In 6 percent of the samples, the concentrations were higher than 130 micromol per L. The highest CO concentration was 561 micromol per L. The main source for these high CO concentrations appeared to be cigarette smoking. In the volunteer smokers, the elimination time after a smoked cigarette varied significantly, with elimination half-lives from 4.7 to 8.4 hours. CONCLUSION: These results show that blood bank red blood cell bags may have CO concentrations above the physiologic level. The time interval between cigarette smoking and blood donation seems to be a particularly important factor for elevated CO concentrations.

Homozygosity for a null allele of SMIM1 defines the Vel-negative blood group phenotype.

The Vel antigen is present on red blood cells (RBCs) from all humans except rare Vel-negative individuals who can form antibodies to Vel in response to transfusion or pregnancy. These antibodies may cause severe hemolytic reactions in blood recipients. We combined SNP profiling and transcriptional network modeling to link the Vel-negative phenotype to SMIM1, located in a 97-kb haplotype block on chromosome 1p36. This gene encodes a previously undiscovered, evolutionarily conserved transmembrane protein expressed on RBCs. Notably, 35 of 35 Vel-negative individuals were homozygous for a frameshift deletion of 17 bp in exon 3. Functional studies using antibodies raised against SMIM1 peptides confirmed a null phenotype in RBC membranes, and SMIM1 overexpression induced Vel expression. Genotype screening estimated that ~1 of 17 Swedish blood donors is a heterozygous deletion carrier and ~1 of 1,200 is a homozygous deletion knockout and enabled identification of Vel-negative donors. Our results establish SMIM1 as a new erythroid gene and Vel as a new blood group system.

Additional molecular bases of the clinically important p blood group phenotype.

BACKGROUND: The purpose of this study was to explore the molecular basis of the p phenotype by analysis of the recently cloned 4-alpha-galactosyltransferase gene responsible for synthesis of Pk (Gb3) antigen. STUDY DESIGN AND METHODS: Forty samples from individuals of eight different nationalities were investigated by serologic methods and DNA sequencing of the Pk gene. RESULTS: Ten different Pk-null alleles, of which 6 are novel, were encountered. The 29 Swedes were homozygous for M183K or G187D, with the former as the predominant allele. Three Israelis were homozygous for a single-nucleotide deletion at codon 219 that shifts and truncates the reading frame by 5 amino acids. Two Italians were homozygous for a triplet deletion causing F81del, while an English donor was heterozygous for F81del but also carried another allele with a combined deletion and insertion. A Pole was heterozygous for alleles with either a single-base deletion at codon 257 or a mutation causing S97L. A Norwegian person and a Japanese person were homozygous for single-base insertions causing a premature stop at codon 282 or extension of the protein by 92 residues, respectively. In 2 samples no mutations were detected. CONCLUSION: The genetic heterogeneity underlying the p phenotype is further emphasized by this study. To date, 11 p-specific mutations have been found in 14 distinct alleles.

The blood group P1 synthase gene is identical to the Gb3/CD77 synthase gene. A clue to the solution of the P1/P2/p puzzle.

Blood group P1/P2 is a glycolipid antigen system for which the genetic mechanism has not yet been clarified. We analyzed the potential of the cloned Gb3/CD77 synthase to synthesize P1 antigen, because Gb3/CD77 and P1 share a common structure, Galalpha1,4Galbeta1,4Glc (NAc)-. L cell transfectants with Gb3/CD77 synthase cDNA expressed marginal levels of P1 on the cell surface but contained high levels of P1 in the cytoplasm. P2-type erythrocytes, which were serotyped as P2, also contained definite P1 antigen inside cells, although the amounts were lower than those of P1 cells. Only p erythrocytes lacked P1 antigen corresponding with function-losing mutations in the Gb3/CD77 synthase gene. Synthesis of P1 antigen from paragloboside in vitro was demonstrated using membrane fraction of the transfectants and a fusion enzyme with protein A. These results strongly suggested that P1 synthase is identical to Gb3/CD77 synthase and appear to propose a clue for the solution of the long-pending P1/P2/p puzzle. The P1/P2 difference might result from the difference in P1 quantity based on either different enzyme activity or the presence/absence of other enzyme modulators. Because P2 erythrocytes showed lower levels of Gb3/CD77 synthase mRNA than P1, 5'-upstream promoter regions were analyzed, resulting in the identification of two P2-specific homozygous mutations. Differences in the transcriptional regulation in erythrocytes might be a major factor determining P1/P2.