Phosphoglucomutase-1 subtypes in the Albanian ethnic minority of the province of Cosenza (Calabria-Southern Italy): Presence of a new variant

Allele frequencies of the phosphoglucomutase-1 (PGM1), in the Albanian ethnic minority of province of Cosenza (Calabria-Southern Italy) were compared with the corresponding data from neighbouring non-Albanian sample groups. The isoelectrofocusing evaluation in the two populations revealed the presence of a new variant PGM1^*W31 in Albanian sample group. Furthermore, a significant heterogeneity was observed between Albanian allele frequencies and those of the surrounding groups.     

A new hereditary variant of the PGM1 erythrocyte enzyme system determined by isoelectric focusing

Summary A new variant of the PGM _a ¹ erythrocyte enzyme system not identical with the known variants of the system has been detected in the hemolyzed red blood cells of a healthy blood donor by isoelectric focusing. Using this technique the variant is represented by two bands, a strong and slow one more cathodically located than the a3 band and a weak one in the position of the a2 band. Using agarose thinlayer or acetate foil electrophoresis the variant is represented only by a minimal cathodic broadening of the PGM₁ 1 band and therefore it is easily overlooked. Investigation of the propositus' family shows that the variant occurs combined with the common alleles PGM ₁ ^a1 , PGM ₁ ^a2 , and PGM ₁ ^a3 and that it has an autosomal dominant inheritance. Obviously the variant has a very low frequency.     

The Russian Gene Pool: Gene Geography of Erythrocytic Gene Markers (ACP1,PGM1,ESD,GLO1, and 6-PGD)

The study continues the series of works on the Russian gene pool. Gene geographic analysis of five erythrocytic gene markers best studied in the Russian population (ACP1, PGM1, ESD, GLO1, and6-PGD) has been performed. Gene-geographic electronic maps have been constructed for 13 alleles of these loci and their correlations with geographic latitude and longitude. For all maps, statistical characteristics are presented, including the variation range and mean gene frequencies, partial and multiple correlations with latitude and longitude, and parameters of heterozygosity and interpopulation diversity. The maps of eight alleles (ACP1*A, ACP1*C, PGM1*2+, PGM1*2–, PGM1*1–, ESD*1, GLO1*1, and PGD*C) are shown and analyzed in detail. The genetic relief and structural elements of the maps are compared with the ecumenical trends, main variation patterns of these genes in northern Eurasia, and genetic characteristics of the indigenous populations of the Urals and Europe.     

Isoelectric focusing of human red cell phosphoglucomutase (PGM1). Phenotype distribution in the population of Tuscany and two hereditary variants

Summary Phosphoglucomutase (PGM₁) phenotypes were determined in a population sample of Tuscany, Italy, by isoelectric focusing. The frequencies observed for the four alleles are: PGM ₁ ¹⁺ =0.6012, PGM ₁ ^1- =0.1059, PGM ₁ ²⁺ =0.2495, PGM ₁ ^2- =0.0434. Two variants were detected and it was possible to study the parentage of both of them. The pedigree of the propositus of the first variant shows that the variant occurs in combination with the common alleles PGM₁ 1+ and PGM₁ 2+ and that it has an autosomal dominant inheritance. The second variant has been shown to be a product of the PGM₂ locus, although its PAGIF pattern is included between 2- and 1+ isoenzymes.     

Investigations on the PGM 1 a polymorphism (phosphoglucomutase-EC 2.7.5.1) by isoelectric focusing

Summary The determination of phosphoglucomutase (PGM₁) phenotypes was performed by isoelectric focusing on samples from 1678 unrelated individuals from Hessen, Germany. Ten common phenotypes are considered as gene products of four alleles at the PGM₁ locus with the following frequencies: PGM ₁ ^a1 =0.6305, PGM ₁ ^a2 =0.1844, PGM ₁ ^a3 =0.1320, and PGM ₁ ^a4 =0.0530. Twenty-two different mating types were observed in 113 families with 202 children. The segregation of the phenotypes in the offspring supports the assumed way of autosomal codominant inheritance. The example of a silent allele (PGM ₁ ⁰ ) as well as a rare variant (PGM ₁ ⁷ ) is reported.     

Population genetics of Glutathione peroxidase (GPX1) in Central Portugal

The isoenzymes of red cell glutathione peroxidase (GPX1) was investigated in the population of Central Portugal. A variant of GPX1 with mobility consistent with GPX1^*2 was detected with a frequency of: GPX1^*2=0,005 (N=221).     

Alpha-1-antitrypsin types in five Chinese national minorities

Summary The frequencies of alpha-1-antitrypsin alleles were determined for five Chinese national minorities: Uigur, Korean, Mongolian, Chuang, and Li. PI^*S and PI^*Z alleles are not found in the five populations studied. PI^*ETOK allele is present in Korean, Mongolian, and Chuang populations, and Etokyo is a very common alpha-1-antitrypsin variant in Chinese. Other alleles which occur in more than one of the minorities are PI^*X (Mongolian and Chuang) and PI^*M4 (Korean and Uigur). The high frequency of PI^*M4 in the Uigur population suggests a probably Occidental origin of this nationality.     

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.     

Evidence for two additional common alleles at the PGM1 locus (Phosphoglucomutase-E.C.:2.7.5.1)

Summary Lysates of erythrocytes, leukocytes, lymphocytes, and extracts of sperms were investigated for the PGM₁ isozymes by three techniques: starch gel electrophoresis, high voltage thin-layer agarose gel electrophoresis, and thinlayer isoelectric focusing on polyacrylamide gel. On starch, only the well known common phenotypes 1, 2-1, and 2 were demonstrable. On agarose, different distances of the two main cathodal bands (a, b) among the phenotypes 2-1 were noted. Furthermore, on agarose, some types considered as homozygous on starch gel had a single, sharp banded pattern, while others were broad and blurred. Optimal separation was achieved by isoelectric focusing on polyacrylamide gel. In 291 leukolysates, 10 different phenotypes were identified. These are considered as gene products of 4 different common alleles at the PGM₁ locus as suggested by preliminary family investigations. In a random population from Hessen these four alleles, had the following frequencies: PGM ₁ ^a1 0.6186, PGM ₁ ^a2 0.1718, PGM ₁ ^a3 0.1426, and PGM ₁ ^a4 0.067. The preliminary designation a1, a2, a3 and a4 was chosen as the assumed polymorphism was demonstrated on acrylamide and agarose. The sum of the frequencies PGM ₁ ^a1 and PGM ₁ ^a3 (the gene products of which have apparently the same electrophoretic mobility on starch) is similar to the frequency of the old PGM ₁ ¹ allele (0.757) in Caucasoids, PGM ₁ ^a2 and PGM ₁ ^a4 have a frequency of 0.2388 corresponding with the frequency of the old allele PGM ₁ ² .     

Red cell glutathione peroxidase (GPX1) variation in Afro-Jamaican,Asiatic Indian,and Dutch populations

Summary A Cellogel procedure for screening the electrophoretic variants of the human red cell glutathione peroxidase (GPX1) was described. Three hundred and ninety eight Dutch persons living in various parts of The Netherlands, 385 individuals born in various states of India, and 72 Jamaicans of African origin livig in Birmingham, UK, were screened for GPX1 variants. The Dutch were monomorphic, while one Afro-Jamaican female and two males and one female of the 116 Punjabis were found to be variants indistinguishable from each other in their pattern of electrophoresis. The clear five banded pattern of the variant indicated that the subunit structure of the human red cell glutathione peroxidase is most probably a tetramer and suggested that the variant is the expression of a heterozygote due to alleles at an autosomal locus. The corresponding phenotype was designated tentatively as GPX1 2-1 and the alleles as GPX1 ^*1 and GPX1 ^*2 respectively. The variant 2-1 was found to be identical to the Thomas variant described by Beutler and West (1974). Thus so far, in addition to the Afro-Americans and Ashkenazi Jews (Beutler et al. 1974), the Punjabis of the Indian subcontinent (this report) were found to exhibit the GPX1 polymorphism due to the GPX1 ^*2 allele. The data discussed in this paper (which included unpublished observations on several African and non-African populations) suggest that the GPX1 ^*2 allele is originally an African variant and hint that the present day Punjabis of Indian subcontinent, like Ashkenazi Jews, are predominantly of Mediterranean origin with some proportion of African ancestry (Mourant et al. 1976).     

Red cell enzyme polymorphisms in Bulgaria

Summary 7 human red cell enzyme polymophisms have been typed on a sample of n=138 unrelated adults from Bulgaria, which revealed the following gene frequencies: ADA¹=0.8623. ADA²=0.1376; AK¹=0.9637, AK²=0.0362; 6-PGD^A=0.9891, 6-PGD^C=0.0108; PGM ₁ ¹ =0.8346, PGM ₁ ² =0.1653; P^A=0.1596, P^B=0.7983, P^C=0.0420. In the LDH-system one B-subunit variant was found, whilst no Peptidase A or B variant could be observed. The anthropological significance of these findings is discussed.

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Zusammenfassung An einer Stichprobe von n=138 nichtverwandten erwachsenen Bulgaren wurden 7 erythrocytäre Enzympolymorphismen untersucht. Dabei ergaben sich die folgenden Frequenzen: ADA¹=0,8623, ADA²=0,1376; AK¹=0,9637, AK²=0,0362; 6-PGD^A=0,9891, 6-PGD^C=0,0108; PGM ₁ ¹ =0,8346, PGM ₁ ² =0,1653; P^A=0,1596, P^B=0,7983, P^C=0,0420. Im LDH-System wurde eine B subunit-Variante gefunden, während keine Peptidase A- oder B-Variante beobachtet werden konnte. Die anthropologische Bedeutung dieser Befunde wird diskutiert.

     

Characterization of mutants of the vitamin D-binding protein/group-specific component: molecular evolution of GC*1A2 and GC*1A3, common in some Asian populations

A well defined polymorphism of vitamin D-binding/ group-specific component (GC) resides in exon 11. To characterize the molecular basis of GC^*1A2 and GC^*1A3, common in some Asian populations, we analyzed all coding exons amplified by the polymerase chain reaction. GC^*1F was divided into GC^*1F^c and GC^*1F^T by a C-T transition in the third nucleotide of the codon (TGC/T) for cysteine²⁸³ in exon 8. The sequencing of exons 8 and 11 showed that GC^*1A2 and GC^*1A3 had occurred on a GC^*1F^c genetic background. They also shared a substitution of cysteine (TGC) for arginine (CGC) at position 429 in exon 11. GC^*1A2 was characterized by having glycine (GGC) instead of serine (AGC) at position 335 in exon 9. GC^*1A2 evolved from GC^*1F^T by three mutational events, i.e. GC^*1F^TGC^*1F^cGC^*1A3 GC^*1A2. No evidence was obtained for the existence of the duplicated gene GC^*1F · 1A2 suggested by isoelectric focusing (IEF) of serum samples. The idea that the characteristic banding pattern of GC^*1F · 1A2 after IEF results from partial formation of a disulfide bond in the additional cysteine at position 429 is discussed.Deceased     

Genetic polymorphism of human complement component C81 in the Japanese population

Summary Genetic polymorphism of human C81 has been investigated using polyacrylamide gel isoelectric focusing (PAGIEF) in the presence of 3.1 M urea followed by electroblotting with enzyme immunoassay. In 448 individuals phenotypes of C81 were classified into three common and four rare patterns, and these were considered to be controlled by two common alleles, C81^*A and C81^* B, and three rare alleles which were tentatively designated C81^*A1J and C81^*A2J for acidic variants and C81^*B1J for the basic variant. The alleles of C81^*A2J and C81^*B1J are new rare alleles, but C81^*A1J might correspond to C81^*A1 in the former studies. Family data were in accordance with the hereditary rules. The gene frequencies were estimated as C81^*A is 0.6228, C81^*B is 0.3672, C81^*A1J is 0.0078, C81^*A2J is 0.0011, and C81^*B1J is 0.0011, respectively. The gene frequencies of the two common alleles agreed approximately with other ethnic groups. PAGIEF of neuraminidase-treated plasma samples followed by electroblotting with enzyme immunoassay is applicable to the study of heterogeneity of C81.     

Orosomucoid (alpha-1 acid glycoprotein) phenotyping by use of immobilized pH gradients with 8M urea and immunoblotting

Summary Orosomucoid (ORM) phenotyping has been performed on 329 unrelated Swiss subjects, using immobilized pH gradients with 8M urea and 2% v/v 2-mercaptoethanol followed by immunoblotting. After desialylation the band patterns of ORM confirmed that the polymorphism of the structural locus ORM1 is controlled by three codominant autosomal alleles (ORM1^*F1, ORM1^*S and ORM1^*F2). One rare and one new allele were detected. The rare variant, tentatively assigned to the second structural locus ORM2, is observed in a cathodal position and named ORM2 B1. The new variant, tentatively assigned to the first structural locus ORM1, is observed in a region located between ORM1 S and ORM1 F2, and named ORM1 F3. Moreover, the pI values of the ORM variants have been measured accurately with Immobiline Dry Plates (LKB): they were found to be within the pH range 4.93–5.14.     

Genetic polymorphism of inter-alpha-trypsin-inhibitor (ITI): Formal genetic and linkage analyses

Summary The polymorphism of inter-alpha-trypsin-inhibitor, ITI, was demonstrated by isoelectric focusing in agarose gels (pH 5–8) followed by protein blotting and immunoassay. Segregation in 239 families with 677 children is consistent with the formal hypothesis that there are two common codominant alleles, ITI^*1, ITI^*2, and one rare codominant allele, ITI^*3, at an autosomal locus ITI. Allele frequencies were calculated as ITI^*1=0.600, ITI^*2=0.393, ITI^*3=0.007. Linkage analysis with 36 markers is presented. Slightly positive lod scores were obtained for PGM3 (z=1,35, =0.10) and AK1 (z=1.34, =0.10).     

Population studies on human phosphoglucomutase-1 thermostability polymorphism

Summary The electrophoretic and thermostability polymorphisms of the PGM ₁ locus were examined in about 700 Czechoslovakians (Prague) and 3000 Italians. The Italian sample consisted of individuals from Pavia (Northern Italy), Viareggio and Rome (Central Italy) and Naples (Southern Italy). The eight PGM ₁ alleles, PGM ₁ ^1Str , PGM ₁ ^1Sts , PGM ₁ ^1Ftr , PGM ₁ ^1Fts , PGM ₁ ^2Str , PGM ₁ ^2Sts , PGM ₁ ^2Ftr , PGM ₁ ^2Fts , have been considered as combinations of mutations at three different sites, 1/2 S/F and tr/ts, within the PGM ₁ gene and their frequencies discussed in terms of linkage disequilibrium between these sites. All pairwise differences between the samples were significant except for Pavia-Viareggio and Viareggio-Rome. The frequencies of the PGM ₁ ^ts alleles have been found to range from 0.0981 (Prague) to 0.0546 (Naples) and can be ordered according to a North-South cline.This paper is dedicated to Professor Giuseppe Montalenti in occasion of his 80th birthday     

Phosphoglucomutase-1 polymorphism among Chinese in Taiwan.

Phosphoglucomutase-1 (PGM1) phenotyping of 1,128 Chinese blood donors was performed by thin-layer isoelectric focusing on agarose. The PGM1 gene frequencies were: 1A, 0.6005; 1B, 0.1500; 2A, 0.1510; 2B, 0.0973, and rare variants, 0.0058. The rare variants found in this series were PGM1 W21, W2, W3, W6 and W9 (or W10) with PGM1 W21 being the most common variant among Chinese with a phenotype frequency of 0.8%.     

Isoelectric focusing of human red cell phosphoglucomutase

Summary A total of 637 individuals from the rural village of Keneba in The Gambia, West Africa, have been typed for red cell PGM using isoelectric focusing (pH 5–7) in polyacrylamide gels. Eight different phenotypes have been detected. The frequency of the four alleles at the PGM₁ locus was found to be PGM ₁ ¹⁺ 0.795, PGM ₁ ^1- 0.053, PGM ₁ ²⁺ 0.133, and PGM ₁ ^2- 0.019. A study of the PGM phenotypes in 89 families confirmed the simple Mendelian codominant inheritance of the four alleles. Comparative population data suggest that red cell PGM typing by isoelectric focusing might prove to be a useful genetic marker in anthropological studies.     

UGT1A1 sequence variants associated with risk of adult hyperbilirubinemia: A quantitative analysis

Backgrounds and Aims

UDP-glucuronosyltransferase 1 A1 (UGT1A1) is an enzyme that transforms small lipophilic molecules into water-soluble and excretable metabolites. UGT1A1 polymorphisms contribute to hyperbilirubinemia. This study quantitatively associated UGT1A1 variants in patients with hyperbilirubinemia and healthy subjects.

Methods

A total of 104 individuals with hyperbilirubinemia and 105 healthy controls were enrolled for genotyping and DNA sequencing UGT1A1 sequence variants, including the Phenobarbital Response enhancer module (PBREM) region, the promoter region (TATA box), and the 5 exons for quantitative association with hyperbilirubinemia.

Results

Eleven UGT1A1 variants were revealed in the case and control subjects, four of which were novel coding variants. A variant of PBREM (UGT1A1*60) was found in 47.6% of the patients, a TA repeat motif in the 5-primer promoter region [A(TA)₇TAA,UGT1A1*28] was found in 27.9% of the patients, and p.G71R (UGT1A1*6) was in 33.2% of the patients. For the healthy controls, the frequency of UGT1A1*60, UGT1A1*28 and UGT1A1*6 was 26.7%, 9.0% and 15.7%, respectively. Homozygous UGT1A1*28 and homozygous UGT1A1*6 were significantly associated with the risk of adult hyperbilirubinemia, with an odds ratio (OR) of 17.79 (95% CIs, 2.11–133.61) and 14.93 (95% CIs, 1.83–121.88), respectively. Quantitative analysis showed that sense mutation (including UGT1A1*6) and UGT1A1*28/*28, but not UGT1A1*60/*60 or UGT1A1*1/*28, was associated with increased serum total bilirubin (TB) levels. High linkage disequilibrium occurred between UGT1A1*60 and UGT1A1*28 (D′ = 0.964, r² = 0.345).

Conclusions

This study identified four novel UGT1A1 coding variants, some of which were associated with increased serum TB levels. A quantitative approach to evaluate adult hyperbilirubinemia provides a more vigorous framework for better understanding of adult hyperbilirubinemia genetics.     

Orosomucoid (ORM) typing by isoelectric focusing: evidence for gene duplication of ORM1 and genetic polymorphism of ORM2

Summary It has been demonstrated that the genetic polymorphism of human serum orosomucoid (ORM) is controlled by polymorphic ORM1 and monomorphic ORM2 loci. In this study a Japanese family was encountered in which several members had puzzling electrophoretic patterns consisting of four bands. The ORM patterns were due to the products of a duplicated ORM1 locus haplotype (ORM1 ^* 2·1) or the products of new variant alleles at the ORM2 locus. The ORM1 ^* 2·1 haplotype is very common in the Japanese population, occurring at an allele frequency of 0.16. The increased occurrence of ORM1 2-1 and the heterogeneity in band intensity among ORM1 2-1 phenotypes could be explained in terms of a duplicated gene ORM1 ^* 2·1. The ORM2 locus proved to be polymorphic, with six alleles in the Japanese population. Dedicated to Professor Dr. K. Nishigami on the occasion of his 60th birthday