The polymorphism of red cell uridine monophosphate kinase in two samples of the Italian population.

Red cell uridine monophosphate kinase polymorphism has been studied on a total of 915 individuals from two different areas of Italy (Milan and Rome). The two groups of about the same size show very similar gene frequencies. The UMPK2 allele in the pooled sample has a frequency of 2.8% which is significantly lower than those observed in the two other Caucasian populations so far examined.     

Glyoxalase 1: a possible 'null' allele.

A three-generation family, ascertained through the presence of two diabetic sibs, provides segregation data suggestive of the existence of a null allele at the glyoxalase (GLO) locus. This conclusion is supported by the GLO 1 phenotype in two children from a GLO 2 father. These two children inherited the same paternal HLA allele, while two other sibs received GLO 2 with the other paternal HLA haplotype. The rest of the pedigree is in agreement with this suggestion, while the segregation of all other informative markers does not suggest nonpaternity.     

Genetic variability inCebus appella paraguayanus: Biochemical analysis of seven loci and variation in Glyoxalase I (E.C.4.4.1.5)

An analysis of seven loci inCebus apella paraguayanus showed that Glyoxalase I was polymorphic due the appearance of two alleles (GLO*2 andGLO*3) with frequencies of 0.955 and 0.045, respectively. Of the two alleles,GLO*2 was electrophoretically similar to the most common allele found in the human andAotus. These results confirmed our previous findings in the same population sample showing that this subspecies has a very low genetic variation among New World primates.     

Glyoxalase 1 (GLO) in the chicken: Genetic variation and lack of linkage to the MHC

Electrophoretic variation of glyoxalase 1 (GLO) has been detected in chicken red-cell lysates. Three phenotypes are shown to be inherited through a diallelic system, just as in humans and mice. The chicken GLO phenotypes differ from their mammalian counterparts in that one of the homozygotes is devoid of GLO activity. The heterozygote produces two bands, while the other homozygote yields a single band of GLO activity with mobility equal to the faster of these two bands. In noninbred White Leghorn birds, the GLO ^*2 allele occurred significantly more often in birds homozygous for the B ^*1 allele at the chicken MHC than in those homozygous for B ^*19, suggesting that the products of these loci may have population associations in the chicken. Absence of close linkage between the GLO and B loci was, however, demonstrated by appropriate test crosses.     

A new variant glyoxalase I allele that is readily detectable in stimulated lymphocytes and lymphoblastoid cell lines but not in circulating lymphocytes or erythrocytes

We describe an allele of the human glyoxalase GLO locus that encodes an enzymatically inactive form of the protein, which would not have been detected if only circulating erythrocytes and lymphocytes had been studied. The new allele is named GLO*3 and its protein product, GLO 3. Circulating blood cells of GLO*2/GLO*3 heterozygotes have just one electrophoretic band that migrates as the normal 2-2 dimer. Lymphoblastoid cell lines and phytohemagglutinin-stimulated lymphocytes from the same individuals have two electrophoretic bands, one with the mobility of the 2-2 dimer and one with the mobility of the 2-1 dimer that is present in GLO*2/GLO*1 heterozygotes, but a band with the mobility of the 1-1 dimer is not present. Therefore, the GLO*3 allele encodes a monomer that has the electrophoretic mobility of GLO 1 but is enzymatically inactive unless it is combined with normal monomers in 2-3 and 1-3 heterodimers. The failure to detect the GLO 3 protein in red cells and unstimulated lymphocytes is attributed to a relatively great instability or small rate of production in those cells. Consistent with this interpretation is the reduction of GLO activity in red cells of GLO*2/GLO*3 and GLO*1/GLO*3 heterozygotes to 65% or less of that in normal homozygotes and heterozygotes, while the activity of GLO*3 heterozygous lymphoblastoid cells is about 80% of normal. In contrast, the GLO activity of lymphoblastoid cells that had one copy of the GLO locus deleted by γ-irradiation was 50%–60% of normal. Our observations indicate that certain kinds of mutant alleles of the GLO locus, and perhaps other loci, may not be detected in electrophoretic surveys on circulating blood cells only. The segregation of alleles that are not expressed in circulating red and white blood cells could confuse attempts to determine parentage, as they might have in the family described here. The observations also demonstrate the feasibility of mapping human genes by using ionizing radiation to create partial chromosome deletions in cultured cells.     

Red-cell enzyme polymorphisms in the Reggio Calabria province (Italy)

Acid phosphatase (ACP1), adenosine deaminase (ADA), esterase D (ESD), glyoxalase 1 (GLO1), phosphogluconate dehydrogenase (PGD) and phosphoglucomutase 1 and 2 (PGM1 and PGM2) polymorphisms have been studied in the Reggio Calabria province (Southern Italy). The ACP1*A allele and ADA, GLO1, PGD and PGM1 systems have frequencies similar to those reported for Sicily and Southern Italy.     

A new rare variant of the glyoxalase I system of the red cell: GLO-Sicily

A fast variant of the red cell enzyme glyoxalase I was identified in a sample of 663 persons from Eastern Sicily; the allele was designated GLOSi. The gene frequencies for the common alleles GLO1 and GLO2 are not different from those observed in other southern Italian populations, and are in agreement with the hypothesis of a westward gene flow from Asia.     

Polymorphism of red cell glyoxalase I (EI: 4.4.1.5); a new genetic marker in man. Investigation of 169 mother-child combinations.

The polymorphism of glyoxalase I was investigated in 169 mother-child combinations from southwestern Germany. Glyoxalase I (GLO) has 3 common phenotypes: GLO 1, GLO 2-1, and GLO 2. The results are in good agreement with the formal hypothesis: Two alleles GLO1 and GLO2 at an autosomal locus. The GLO1 gene frequency was estimated to be 0.39. From the electrophoretic pattern the GLO-molecule appears to consist of two subunits.     

Genetic polymorphism of blood group and erythrocyte enzymes in three ethno-territorial groups of the northern European part of Russia]

Using the data on five red cell markers (AB0, PGM1, ACP1, GLO1, and ESD) polymorphisms, the population genetic structure of three ethnic territorial groups from the north of European Russia (Continental Nentsy, Kola Saami, and Russian Coast-dwellers) was described. In general, the groups studied a Caucasoid pattern of the frequency distribution of erythrocytic marker alleles. However, a substantial contribution of a Mongoloid component to the Nenets gene pool, expressed as a high frequency of the PGM1*1 allele along with a low frequency of the GLO1*1 allele, was observed. Three ethnic territorial groups examined were close to one another with respect to the distribution of classical biochemical markers. The interpopulation diversity was low (the mean FST = 0.015). The differences observed were for the most part caused by the genetic characteristics of Nentsy. The maximum interpopulation diversity was observed for the GLO1 locus (FST = 0.056).     

Red cell enzyme polymorphisms in Moroccans and southern Spaniards: new data for the genetic history of the western Mediterranean.

Population samples from Morocco (El Jadida, south Atlantic coast) and La Alpujarra (Granada mountains, Spain), located on both shores of the western Mediterranean, were typed for 8 erythrocyte genetic markers: ACP1, ESD, PGD, AK1, GLO1, PGM1, SODA, and DIA. Genetic heterogeneity within western Mediterranean groups was investigated on the basis of allele frequencies of these 8 polymorphisms plus ABO and Rh (CDE). Only slight peculiarities for the ACP1, GLO1, and AK1 systems were observed in the 2 samples compared with other Mediterranean data. The new data are consistent with a main north to south genetic differentiation in the Mediterranean region. However, with regard to other European groups, the La Alpujarra population shows a particular affinity with North Africans that may be compatible with both an ancient common substratum and/or a special historical influence during the Muslim domination of the Iberian Peninsula.     

Genetic Polymorphism of the Blood Groups and Erythrocytic Enzymes in Three Ethnic Territorial Groups from the North of European Russia

Using the data on five red cell markers (AB0, PGM1, ACP1, GLO1, and ESD) polymorphisms, the population genetic structure of three ethnic territorial groups from the north of European Russia (Continental Nentsy, Kola Saami, and Russian Coast-dwellers) was described. In general, the groups studied a Caucasoid pattern of the frequency distribution of erythrocytic marker alleles. However, a substantial contribution of a Mongoloid component to the Nenets gene pool, expressed as a high frequency of the PGM1*1allele along with a low frequency of the GLO1*1allele, was observed. Three ethnic territorial groups examined were close to one another with respect to the distribution of classical biochemical markers. The interpopulation diversity was low (the mean F _ST= 0.015). The differences observed were for the most part caused by the genetic characteristics of Nentsy. The maximum interpopulation diversity was observed for the GLO1*locus (F _ST= 0.056).     

Genetic predisposition to development of toxic liver cirrhosis caused by alcohol]

Comprehensive analysis of the contribution of genetic factors into predisposition to alcoholic toxic cirrhosis (TC) was performed. The ABO, RH, HP, TF, GC, PI, ACP1, PGM1, ESD, GLO1, and GST1 genetic polymorphisms were compared in 34- to 59-year-old male TC patients and control donors of the same sex and age. The phenotypic frequencies in the TC group deviated from the theoretically expected values; the main difference was the excess of rare homozygotes for the loci GC, ACP1, ESD, and GLO1. In the TC patients, the observed heterozygosity (Ho) was considerably lower than the theoretically expected value (H(e)). Wright's fixation index (F) in the TC patients was 30 times higher than in the control group (0.0888 and 0.0027, respectively). The frequencies of PI*Z and PI*S, the PI alleles that are responsible for lower concentrations of proteinase inhibitor, were 12 and 6 times higher in the TC than in the control group. The TC patients exhibited a significantly higher frequency of the liver glutathione-S-transferase GST1*0 allele, whereas the GST1*2 frequency was two times higher in the control subjects than in the TC patients (0.2522 and 0.0953, respectively). The TC and control groups showed statistically significant differences in the frequencies of the following alleles of six independent loci: ABO*0, TF*C1, TF*C2, PI*M1, PI*Z, ACP1*C, PGM1*1+, PGM1*1-, PGM1*2-, GST1*0, and GST1*2. The haptoglobin level was significantly higher and the serum transferrin level was drastically lower in all phenotypic groups of TC patients than in control subjects. The concentrations of IgM and IgG depended on the HP, GC, and PI phenotypes. The total and direct reacting bilirubin concentrations depended on the erythrocytic-enzyme phenotypes (ACP1, PGM1, and GLO1) in both TC and control groups.     

Effects of potassium,lanthanum and black widow spider venom on miniature synaptic potentials in theTorpedo electroplax

Summary Using a method of focal drug application it is demonstrated that high potassium concentration, lanthanum, and black widow spider venom accelerate spontaneous transmitter release inTorpedo electric tissue.This investigation was supported by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 138). Thanks are due to Dr. R. Martin and the staff of the Stazione Zoologica, Naples, for supplyingTorpedo, and Dr. N. Frontali, Rome, for a gift of frozen black widow spiders.     

Human red cell glyoxalase I polymorphism in Denmark and its application to paternity cases.

Phenotypes of glyoxalase I (GLO) were determined in 1220 unrelated adults from all parts of Denmark giving the gene frequencies GLO1 = 0.4311 and GLO2 = 0.5689. The segregation of phenotypes in 59 families and in 455 mother-child pairs was consistent with the assumed autosomal codominant inheritance. The results of an investigation of 379 parternity cases with respect to exclusions of non-fathers by means of the GLO system are reported, and the application of the GLO system to paternity cases is discussed.     

Glyoxalase I polymorphism in South African Bantu-speaking Negroids

Summary The newly described genetic polymorphism of glyoxalase I (GLO) is studied in seven ethnically defined Negroid samples from South Africa (total: n=843). The allele frequencies between the different Negroid samples studied vary only marginally. However, the allele frequency of GLO¹ for the South African Negroid samples combined (i.e., p=0.259), is highly significantly lower than that for Caucasoid samples.Supported by the Deutsche Forschungsgemeinschaft (DFG), Bonn-Bad GodesbergSupported by a research fellowship (1975/76) awarded by the Alexander-von-Humboldt-Stiftung, Bonn-Bad Godesberg     

Linkage of GLO with HLA in a sample of the Spanish population

Summary GLO allele frequencies are studied in 100 unrelated normal Spaniards. GLO-S shows a frequency similar to that found in Caucasoids. Weak linkage disequilibria between some HLA-B and some HLA-DR antigens are described. DR3 and DR4 are GLO-F associated both in normal and insulin dependent diabetic Spaniards. GLO/HLA-DR loci distance is about 6cM according to our family studies; females show a higher GLO/HLA-DR recombination rate than males in our sample. NO GLO heterozygous excess or nul alleles are found.     

Genetic Predisposition to Alcoholic Toxic Cirrhosis

Comprehensive analysis of the contribution of genetic factors into predisposition to alcoholic toxic cirrhosis (TC) was performed. The AB0, RH, HP, TF, GC, PI, ACP1, PGM1, ESD, GLO1, and GST1 genetic polymorphisms were compared in 34- to 59-year-old male TC patients and control donors of the same sex and age. The phenotypic frequencies in the TC group deviated from the theoretically expected values; the main difference was the excess of rare homozygotes for the lociGC, ACP1, ESD, and GLO1.In the TC patients, the observed heterozygosity (H _o) was considerably lower than the theoretically expected value (H _e). Wright's fixation index (F) in the TC patients was 30 times higher than in the control group (0.0888 and 0.0027, respectively). A considerable decrease in the ABO*0allele frequency at the expense of an increase in the ABO*Aallele frequencywas observed in the TC patients as compared to the control sample. The TF*C2allele frequencywas two times higher in the patients than in the control group (0.2571 and 0.1308, respectively). The frequencies ofPI*Zand PI*S, the PIalleles that are responsible for lower concentrations of proteinase inhibitor, were 12 and 6 times higher in the TC than in the control group. The TC patients exhibited a significantly higher frequency of the liver glutathione-S-transferase GST1*0allele, whereas the GST1*2frequency was two times higher in the control subjects than in the TC patients (0.2522 and 0.0953, respectively). The TC and control groups showed statistically significant differences in the frequencies of the following alleles of six independent loci: ABO*0, TF*C1, TF*C2, PI*M1, PI*Z, ACP1*C, PGM1*1+, PGM1*1–, PGM1*2–, GST1*0, andGST1*2. The haptoglobin level was significantly higher and the serum transferrin level was drastically lower in all phenotypic groups of TC patients than in control subjects. The concentrations of IgM and IgG depended on the HP, GC, and PI phenotypes. The total and direct reacting bilirubin concentrations depended on the red cell-enzyme phenotypes (ACP1, PGM1, and GLO1) in both TC and control groups.     

Airport and city-centre temperatures in the evaluation of the association between heat and mortality

A variety of ambient exposure indicators have been used to evaluate the impact of high temperature on mortality and in the identification of susceptible population sub-groups, but no study has evaluated how airport and city centre temperatures differ in their association with mortality during summer. This study considers the differences in temperatures measured at the airport and in the city centre of three Italian cities (Milan, Rome and Turin) and investigates the impact of these measures on daily mortality. The case-crossover design was applied to evaluate the association between daily mean apparent temperature (MAT) and daily total mortality. The analysis was conducted for the entire population and for subgroups defined by demographic characteristics, socioeconomic status and chronic comorbidity (based on hospitalisation during the preceding 2 years). The percentage risk of dying, with 95% confidence intervals (95% CI), on a day with MAT at the 95th percentile with respect to the 25th percentile of the June-September daily distribution was estimated. Airport and city-centre temperature distributions, which vary among cities and between stations, have a heterogeneous impact on mortality. Milan was the city with the greatest differences in mean MAT between airport and city stations, and the overall risk of dying was greater when airport MAT (+47% increase, 95%CI 38-57) was considered in comparison to city MAT (+37% increase, 95%CI 30-45). In Rome and Turin, the results were very similar for both apparent temperature measures. In all cities, the elderly, women and subjects with previous psychiatric conditions, depression, heart and circulation disorders and cerebrovascular disease were at higher risk of dying during hot days, and the degree of effect modification was similar using airport or city-centre MAT. Studies on the impact of meteorological variables on mortality, or other health indicators, need to account for the possible differences between airport and city centre meteorological variables in order to give more accurate estimates of health effects.     

Flow cytometric analysis of glyoxalase-1 expression in human leukocytes

Altered glyoxalase‐1 (GLO‐1) activity and expression is associated with the development of late diabetic complications, malignancy and oxidative stress‐ and aging‐related diseases. In the present study, we developed a flow cytometry method for GLO‐1 detection in human leukocytes isolated from peripheral blood samples to investigate GLO‐1 expression in leukocyte subsets from type 1 and 2 diabetes mellitus patients (n = 11) and healthy subjects (n = 8). The flow cytometry analysis of GLO‐1 in leukocytes showed that expression index of GLO‐1‐positive cells was slightly increased in mononuclear leukocytes from diabetic patients. This result correlated with the increase in GLO‐1 activity in the whole blood samples of type 2 diabetes patients. In conclusion, the present study demonstrates that flow cytometry is suitable for the detection of the GLO‐1 enzyme in human leukocytes and that this method could be used to investigate the fast adaptation of the glyoxalase system related to the pathogenesis of late complications of diabetes mellitus and other glycation stress‐related disorders. Copyright © 2011 John Wiley & Sons, Ltd.