Serumprotein polymorphisms in Iran

Summary The results of a population genetic investigation on Iranians are given and compared to the results obtained on other populations from Southwestern and Southern Asia. Our total material from Iran comprises n=1020 nonrelated male and female individuals of different age. The following serum groups have been typed: Hp, Gc, Gm, and Inv. In general there exist no remarkable age or sex differences in the distribution of phenotypes and alleles (the only exception: sex differences in the distribution of the Gm (7)-phenotype). The regional distribution of phenotypes and alleles yield no marked differences, too, apart from the Invphenotypes, however. For the total material of Iran the following alleles frequencies could be calculated: Hp¹=0.3045, Hp²=0.6595, Gc²=0.3405; Gm¹=0.1780, Gm^1,2=0.0537, Gm^1,5=0.0632, Gm⁵=0.7051. The Gm (7)-phenotype turned out to be 36.6%; the Inv (1)-phenotype amounts to 25.6%. Comparing with other populations, especially Pakistani and Indian samples, some heterogeneity in the distribution of phenotypes and alleles within Southwestern and Southern Asia was to be demonstrated. Some distributional trends of alleles frequencies shall be mentioned here: the increase of Hp², Gc¹, and Gm¹ alleles from West towards East, and in the opposite direction the decrease of Hp¹, Gc², and Gm⁵ alleles. Selective acting forces are supposed to be most important factors for this. D77     

Distribution of the group specific (Gc) serum component in the populations of the Markham Valley, New Guinea

The distribution of the Gc phenotypes was determined by immunoelectrophoresis amongst 486 inhabitants of nine villages of the Markham River Valley of New Guinea. The overall gene frequencies were Gc¹, 0.538; Gc², 0.351; Gc^Aborigine, 0.112. Gc^Aborigine occurred in all the villages, its frequency ranging from 0.041 to 0.187. The Gc² gene frequency also varied widely ranging from 0.167 to 0.491. No correlation could be found between altitude and the Gc distribution and there was an overlap in the gene frequencies between the Austronesian and non-Austronesian-speaking villages.     

Untersuchungen zur Populationsgenetik von Island,insbesondere der Region Dalasýsla

The authors report the results of a population genetic survey of the Dalasýsla region (West-Iceland). Our sample size includes n=193 male and female individuals of different age. These individuals are partly related. The following blood and serum groups were determined: ABO, MNS, Rh, P; Hp, Gc, Gm, InV, and Lp. In all these systems observed and expected phenotype frequencies are found to be in good agreement. The following gene frequencies turned out: p₁ ^A=.0888, p₂ ^A=.0456, q^B=.0293, r^O=.8363; p^MS=.2256, p^Ms=.4474, p^NS=.0540, p^Ns=.2730; cde=.4123, Cde=.0966, cDe=.0338, CDe=.2984, cDE=.1589; p^P=.4833; Hp¹=.5157, Hp²=.4843; Gc¹=.7340, Gc²=.2660; Gm¹=.1846, Gm^1,2=.1444, Gm¹²=.6710. The frequency of the phenotype InV (1) comes to 17,6%, that of Lp (a+) amounts to 21,6%.In general the Icelandic phenotype and allele frequencies correspond to the European ones, especially to those observed in Northern Europe. In connection with this the authors discuss briefly, to what extent the present day phenotype distributions (especially concerning the ABO system) of Iceland may be interpreted with regard to historical facts and events. It is pointed out that at any rate also selective acting factors should be taken into consideration in order to interpret really the present day distributions. Within Iceland certain inhomogeneities in the phenotype distributions are present. Factors such as small population sizes, geographical isolation, and gene-drift are most likely responsible for this.     

Zur Häufigkeit der Serumprotein-Polymorphismen Hp,Gc, Gm,InV und Lp in Griechenland

The authors report the frequencies of Hp-, Gc-, Gm-, InV-, and Lp-phenotypes and alleles in a Greek sample of 218 unrelated adult males and females. The following gene-frequencies were obtained: Hp¹=.2850, Hp²=.7150; Gc¹=.7590, Gc²=.2410; Gm¹=.1555, Gm^1,2=.1015, Gm¹²=.7430. The phenotype InV (1) was found to be 14.6%. Lp (ax)-typing showed 17.0% strong positive individuals, 9.7% weak positive ones, and 73.3% negatives. According to Speiser and Pausch (1965) this may be interpreted as the following phenotypes distribution: Lp (a+x+)=17.0%, Lp(a+x-)=9.7%, and Lp(a-x-)=73.3%. Our data differ somewhat from data obtained by other authors, which seems to indicate heterogeneity in the distribution of at least Hp- and Gm-phenotypes within the Greek population. This is project to further research.     

Häufigkeit der Sichttypen in den Erbsystemen Haptoglobin,Gc, saure Erythrocytenphosphatase,Phosphoglucomutase und Adenylatkinase sowie den Erbeigenschaften Gm(1), Gm(2) und Inv(1) bei Deutschen (aus dem Raum Freiburg i. Br. und Köln) und bei Türken

Zusammenfassung Die an 274 Türken und einer mehrfachen Zahl Deutscher (787–5030) durchgeführten Untersuchungen ergaben eine etwas größere Häufigkeit des Gens Hp¹ im Raum Köln und eine größere des Gens Inv¹ im Raum Freiburg i. Br. Bei Türken sind die Allele Hp², Gm¹, P^b und PGM² häufiger, die Allele Hp¹, Gm^1,2, P_a, P_c und PGM¹ seltener als bei Deutschen. Die Frequenzen im Gc- und AK-System stimmen überein.

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Summary There was found a higher frequency of Hp¹ and a lower of Inv¹ in the population of Cologne than in the population of Freiburg. The frequencies of Hp², Gm¹, P^b and PGM² in the Turkish population were found to be higher than those in the German population; the frequencies of Hp¹, Gm^1,2, P^a, P^c and PGM¹ were found to be lower. In the systems Gc and AK the frequencies in the two populations are not significantly different.

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(Direktor: Prof. Dr. R. Haas)

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(Direktor: Prof. Dr. G. Pulverer)

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(Direktor: Prof. Dr. C. Bennholdt-Thomsen)     

The distribution of Gc subtypes among the Mongoloid populations

The polymorphism of Gc (group-specific components) has been investigated for a series of 3,160 individual samples from 11 Mongoloid populations in Asia and North and South America by isoelectric focusing on polyacrylamide gels. The samples fall into six Gc phenotypes which can be explained by the three common alleles, Gc^1F, Gc^1S, and Gc², together with several variant phenotypes explained as the heterozygotes for the three common alleles. The distribution of Gc^1F suballele appears to be considerably different from population to population among Mongoloids, ranging from 0.105 (Machiguenga Indans, Peru) to 0.609 (Kadazan, Borneo). A clear geographic cline from Southeast Asia into South America in Gc^1F allele was observed in the populations. In general, Gc^1F allele frequencies are lower in European populations and higher in African populations. The range of variability in the Gc^1F values observed among the Asiatic populations is between the Africans and the Europeans.     

Group-specific component (Gc) subtypes in the Chinese population of Hong Kong

Summary The distribution of Gc subtypes in a sample of the Chinese population of Hong Kong was studied using isoelectric focusing followed by immunofixation. A sensitive modification of this technique is described. Nine distinct phenotypes were observed which appear to result from the three common alleles Gc ^IF, Gc ^IS, and Gc ², which are found in most populations. The respective gene frequencies were 0.494, 0.258, and 0.247. In addition, two rare phenotypes were observed which appear to be due to a rare allele tentatively identified as Gc ^2G2.     

Gc (vitamin D binding protein) subtype polymorphism and variants distribution among Saharan,Middle East,and African populations

This article presents the results obtained by electrophoretic analysis of the group specific component polymorphism in more than 1,250 serum samples from populations living in the Sahara, the Middle East, and equatorial Africa. In addition to the alleles Gc^IF and Gc^IS, five variants, including one previously unknown, were found. The distribution of the alleles herein described permits speculation on exchanges and relation among the groups considered. The lowest frequencies of the gene Gc² correspond to regions where sunlight is stronger. There is also a north-south gradient in the Gc^IF gene frequency. This seems to parallel the gradient seen in skin pigmentation.     

Role of Haptoglobin in Polycystic Ovary Syndrome (PCOS), Obesity and Disorders of Glucose Tolerance in Premenopausal Women

Background

Hp² alleles of the haptoglobin α–chain polymorphism reduce the anti-oxidant properties and increase the pro-inflammatory actions of this acute-phase protein in a gene-dosage fashion. We hypothesized that the haptoglobin polymorphism might contribute to the increased oxidative stress and low-grade chronic inflammation frequently associated with polycystic ovary syndrome, obesity, and abnormalities of glucose tolerance.

Methodology/Principal Findings

Serum haptoglobin and the haptoglobin α–chain polymorphism were determined in 141 patients with polycystic ovary syndrome and 102 non-hyperandrogenic women. Of the whole group of 243 premenopausal women, 117 were obese and 51 showed abnormal glucose tolerance. Although serum haptoglobin concentrations were similar in PCOS patients and controls, the former presented with an increased frequency of Hp² alleles (62% vs. 52%, P = 0.023). Circulating haptoglobin levels increased with obesity (P<0.001), yet no association was found between obesity and haptoglobin genotypes. No differences were observed in haptoglobin levels or genotype frequencies depending on glucose tolerance. Fifty percent of the variation in serum haptoglobin concentrations was explained by the variability in serum C-reactive protein concentrations, BMI, insulin sensitivity and haptoglobin genotypes.

Conclusions/Significance

Serum haptoglobin concentrations in premenopausal women are largely dependent on the haptoglobin polymorphism and on the presence of obesity, with insulin resistance and chronic inflammation possibly modulating this relationship. The association of polycystic ovary syndrome with Hp² alleles suggests that the anti-oxidant and anti-inflammatory properties of haptoglobin may be reduced in these patients.     

Intra and intertribal genetic variation within a linguistic group: The Ge-speaking Indians of Brazil

A total of 562 individuals living in four villages of two Brazilian Indian tribes (Cayapo and Krahó) was studied in relation to blood groups ABO, MNSs, P, Rh, Lewis, Duffy, Kidd and Diego; haptoglobin, Gc, acid phosphatase and phosphoglucomutase types. These results were compared with those obtained previously among the Xavante, and the inhabitants of three other Cayapo villages, all of whom speak Ge languages; the ranges in gene frequencies observed in a representative series of South American Indians from all over the continent were also compiled. The Ge Indians are characterized by low frequencies ofR^z, medium frequencies ofR¹,R², R⁰, orr,Jk^a andPGM¹₁, and high frequencies ofGc² andACP^A when compared with other South American tribes. Genetic distance analyses based on six loci indicate that the intratribal variability observed among Cayapo is of the same order of magnitude as those obtained among the Xavante and Krahó, being much less pronounced than those observed among the Yanomama and Makiritare. The intertribal differences within this linguistic group are much less pronounced than those encountered among tribes that speak more differentiated languages.     

The distribution of haptoglobin and transferrin types in northeast New Guinea

This paper reports haptoglobin testing of 2,029 serum specimens and transferrin typing of 1,911 specimens obtained from villages representing a wide range of environments and cultures in the Markham River Valley region of northeast New Guinea. The haptoglobin gene frequencies ranged from 90.0% to 61.4% for Hp¹ and the frequency of the transferring gene Tf^c ranged from 94.9% to 71.5%. Other transferrin genes present were Tf^D1 and, in low frequency, Tf^{B Lae}. Overall, no apparent correlations were found between the frequencies of these genes and altitudes, languages or distances of the villages studied up the valley. It was felt that the arguments put forward earlier emphasizing the role of genetic drift in determining gene distribution in New Guinea could be also applied to explain the distribution of the haptoglobin and transferrin genes in the Markham River Valley.     

Hemoglobins, haptoglobins, and transferrins in indigenous populations of Kenya

Hemoglobin, haptoglobin, and transferrin phenotypes were determined by means of starch-gel electrophoresis for a sample of 226 Kenya hospital patients. Allele frequencies were: Hb_β^S=0.081; Hp¹=0.057; Tf^D=0.038. Hemoglobin S was the only aberrant hemoglobin found in this sample. Transferrins C and D were the only transferrins found. Hemoglobin and transferrin phenotypes were also determined for a sample of 201 newborn Kenya infants. One of these infants had hemoglobins F, S, and C, eight had hemoglobins A, F, and S, and the remainder had hemoglobins A and F. Transferrins C, B, and D were found in this sample. Allele frequencies were: Tf^B=0.008; Tf^D=0.019.     

Distribution of blood groups among indians in South America. VI. In Paraguay

This paper on the distribution of hereditary factors in the blood of Indians in South America, reports the results of tests made on samples procured from Paraguayan Indians. Specimens from putatively full-blood persons were obtained from the following tribes: 88 Chamacoco, 36 Moro, 85 Chulupi, 207 Lengua, 100 Toba, 20 Yam Lengua, and 51 Guayaki, These 587 Samples were tested for factors in the A-B-O, M-N-S-s, P. Rh-Hr, Lutheran, Kell-Cellano, Lewis, Duffy, Kidd, and Diego systems. Serum samples were tested for haptoglobins and transferrins. He molysates, prepared from whole blood, were tested for hemoglobin types. The results are presented on appropriate tables as number and per cent of phenotypes for the various blood group antigens and their calculated allele frequencies. Locations of the populations from which blood samples were procured are listed on the tables and shown on a map (fig. 1). Of the 587 samples all except two Chamacoco belonged to group O. High frequencies are reported generally for M, s, P, R¹ (CDe), R² (cDE), k (100%) and Fy alleles in Paraguayn Indians. Low frequencies were generally reported for N, S, r (cde) and R° (cDe) alleles. There was a wide variation in frequencies for Di, Jk, and haptoglobin Hp¹. All tested for transferrins were classified as Tf C and all contained hemoglobin (A) as a major component. The following antigens were completely absent: Mi^a, Vw, p, P^k, r^y (CdE), K, and Le¹. Most notable is the unusual distribution of hereditary blood antigens among the Guayaki and Moro. The Guayaki had 100% P₁ and Fy^a; they were higher in R° (cDe), R¹ (CDe), and Jk^a; and lower in R² (cDE) and Hp¹ genes than other Indians; and Di was absent. The Guayaki differed from the other Indians also in having fair skin. The Moro were lower in the P¹ and Jk gene frequencies than is usually found in Amerinds, and the Di gene was absent. The Chamacoco also had an exceptionally low frequency for the P¹ gene (0.261).     

Human transferrin (Tf) and group-specific component (Gc) subtypes in Tunisia

Summary Simultaneous subtyping of two genetic markers—group-specific component (Gc) and transferrin (Tf)—by electrofocusing enabled us to compute the following gene frequencies for the Tunisian population: Gc ^IS .0.525; Gc ^IF , 0.260; Gc ², 0.215; Tf ^CI , 0.770; Tf ^C2 , 0.215; Tf ^D1 , 0.015.The frequencies of Tf ^D , Tf ^C2 , and Gc ¹ are higher than those found in Caucasoid populations and can be explained by Negroid contribution. A selective advantage related to the metabolic role of this vitamin D-binding protein does not seem very likely for any particular Gc type or subtype. It is postulated that the differences in the frequencies of the Gc alleles might be related to selective advantage for genes belonging to other genetic systems originally closely linked to either Gc ¹ or to Gc ² alleles.This work was supported in part by the Faculté de Pharmacie et de Médecine Dentaire of Monastir and by a grant from the Ambassade de France in Tunisia     

Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene

Summary. In this study we focused on detecting schizophrenia related changes of plasma proteins using proteomic technology and examining the relation between schizophrenia and haptoglobin (Hp) genotype. We investigated plasma proteins from schizophrenic subjects (n = 42) and healthy controls (n = 46) by two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry. To further reveal the genetic relationship between acute phase proteins (APPs) and schizophrenia disease, we tested Hp α1/Hp α2 (Hp 1/2) polymorphism and two single nucleotide polymorphisms (SNPs) of Hp, rs2070937 and rs5473, for associations with schizophrenia in the Chinese Han population. With the relatively high number of samples for 2-DE work, we found that four proteins in the family of positive APPs were all up-regulated in patients. In genetic association study, we found significant associations existing between schizophrenia and Hp polymorphisms, Hp 1/2 and rs2070937 variants. Schizophrenia is accompanied by both an altered expression of Hp protein and a different genotype distribution of Hp gene, demonstrating that Hp is associated with schizophrenia. The results from proteomic and genomic aspects both indicate that acute phase reaction is likely to be an aetiological agent in the pathophysiology of schizophrenia, but not just an accompanying symptom. The positive APPs are schizophrenic related proteins, with the highly concordant results on four positive APPs. The first two authors contributed equally.     

A faster migrating Gc-variant: Gc Darmstadt

Summary In three members of a family from Darmstadt (Germany) a faster migrating Gc variant has been observed. The variant phenotypes have been examined by routine immunoelectrophoresis (Fig. 1), by immunoelectrophoresis with prolonged separation times and with Gc-monospecific antisera (Fig. 2), by polyacrylamide gel electrophoresis (Fig. 3), and by antigen-antibody crossed electrophoresis (Fig. 4). By antigen-antibody crossed electrophoresis the new Gc variant was clearly distinguishable from the Gc Aborigine and from the Gc Chippewa variant. The variant was named Gc Darmstadt (Gc D). Gc Darmstadt has an electrophoretic migration rate intermediate between Gc Ab and Gc 1. In two sibs the type Gc D-2 was observed, the daughter of one of these sibs had the type Gc D-1. The analysis of several members of this family provided only limited information on the mode of inheritance of Gc Darmstadt (Fig. 5). Gc Darmstadt appears to be determined by a gene Gc^D which may be allelic to Gc¹ and Gc².

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Zusammenfassung Bei drei Angehörigen einer Familie aus Darmstadt (Deutschland) wurde eine schneller wandernde Gc-Variante beobachtet. Die neue Variante, die eindeutig von Gc Aborigine und Gc Chippewa unterschieden werden kann, wurde Gc Darmstadt (Gc D) genannt. Bei elektrophoretischer Auftrennung liegt Gc Darmstadt zwischen Gc Ab und Gc 1. Gc Darmstadt ist sehr wahrscheinluch durch ein Gen Gc^D bedingt, das ein Allel zu Gc¹ und Gc² ist.

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Supported by U.S.-PHS Grant AM 11796 and aided by a grant from the Deutsche Forschungsgemeinschaft, Bad Godesberg.     

Haptoglobin,transferrin and serum albumin variants in the Dayaks of Sarawak

Summary The Land Dayaks and the Sea Dayaks of Sarawak were surveyed for haptoglobin, transferrin and serum albumin variants. The Hp¹ gene frequency was 0.385 in 283 Land Dayaks as well as in 205 Sea Dayaks. The TfD_Chi gene frequency in 283 Land Dayaks was 0.030 and in 188 Sea Dayaks it was 0.040. Serum albumin Medan was found in one of the 188 Sea Dayaks.This work was supported in part by the University of California International Center for Medical Research (UC ICMR) through research grant AI 10051, and in part by research grant HL 10486, both from the National Institutes of Health, U.S. Public Health Service.     

Restriction and persistence of polymorphisms of HLA and other blood genetic traits in the Parakanã Indians of Brazil

Results concerning HLA types and 22 other blood genetic systems are reported for the Parakanã Indians of northern Brazil, a tribe that is notable for the light color and pilosity of some of its members. No clear evidence of Caucasoid admixture was found, but the Parkanã show unusual frequencies in the EsD¹, PGM¹₁, Gc², Cp^B, Fy^a, Di^a, and L^M genetic markers. In addition, the very rare Rh allele r^y is present, as well as what seems to be a new PGM₂ variant. There is very limited heterogeneity in the HLA system. All these distinctive features may have arisen through a combination of founder effects and genetic drift. However, low F_is values, as well as higher mean ages in heterozygous as compared to homozygous persons, suggest that an heterotic effect is counteracting these dispersive forces.     

Consequences of haemolysis without haptoglobin

Abstract

Haptoglobin (Hp), a conserved plasma glycoprotein, forms very stable soluble complexes with free plasma haemoglobin. Haemoglobin binding by haptoglobin is thought to be important in the rapid hepatic clearance of haemoglobin from the plasma and in the inhibition of glomerular filtration of haemoglobin. It is thought to reduce haemoglobin-induced renal damage during haemolysis. To evaluate these functions, Hp knockout (Hp^-/-) mice were created. The Hp^-/- mouse was generated by a standard gene replacement technique in mouse embryonic stem cells. These mice were evaluated with and without haemolysis using several parameters: mortality, haemoglobin clearance, renal tissue damage and function.

Hp^-/- mice were viable but had a small, significant reduction in postnatal viability. The lack of Hp did not impair clearance of free plasma haemoglobin. Induction of severe haemolysis by phenylhydrazine caused extensive haemoglobin precipitation in the renal tubular cells. However, haemoglobin precipitation in the kidney was not increased in Hp^-/- mice. Nevertheless, Hp^-/- mice were more susceptible to phenylhydrazine with a mortality rate of 55% in Hp^-/- mice versus 18% in Hp^+/+ mice. In general, phenylhydrazine-treated Hp^-/- mice suffered greater tissue damage, as evidenced by the induction of a hepatic acute phase response, resulting in increased plasma₁-acidic glycoprotein (AGP) levels and higher plasma malonaldehyde (MDA) and 4-hydroxy-2(E)-nonenal (HNE) levels. Gross pathological analysis indicated that the kidney was the most affected tissue in phenylhydrazine-treated Hp^-/- and Hp^+/+ mice, and Hp^-/- mice were more severely affected. They had lower mitotic indices in their kidneys, higher basal levels of renal lipid peroxidation, as evidenced by levels of malonaldehyde and 4-hydroxy-2(E)-nonenal (MDA/HNE) and elevated levels of 8-hydroxyguanine (but not other products of oxidative DNA damage). There also was increased induction of haem oxygenase-1. The more severe renal damage in Hp^-/- mice was also evident in the delayed erythropoietin gene expression and poorer renal clearance of [³H]-inulin. The reduction in glomerular filtration function in Hp ^+/+ and Hp^-/- mice could be restored to baseline by vasodilators (prazosin or diazoxide), implicating renal vasoconstriction as a major mechanism of acute renal failure during induced haemolysis.

These data suggest that Hp plays a pivotal role in reducing renal oxidative damage during haemolysis.     

ABO,Rh(D) and haptoglobin distribution in a sample from the sultanate of Oman

The distribution of phenotypic frequencies of ABO, Rh(D) system and Hp polymorphism in a sample from Muscat, Oman, revealed the following gene frequencies: P=0.164, q=0.110, r=0.726; D=0.738, d=0.262; Hp¹=0.289 and Hp²=0.711. These frequencies are in good agreement with the distribution in the Euroasiatic continent.