[Adrenoleukodystrophy and adrenomyeloneuropathy. Clinical biochemical and molecular genetic findings]. / Adrenoleukodystrophie und Adrenomyeloneuropathie. Klinische, biochemische und molekulargenetische Befunde.

Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disease affecting 1 in 20,000 males either as cerebral ALD in childhood or as adrenomyeloneuropathy (AMN) in adulthood. Recently, the ALD gene has been identified by positional cloning. We report three males patients with AMN and a fourth patient with juvenile ALD. Biochemical studies showed elevated plasma concentration of saturated very-long-chain fatty acids. Genomic DNA of the patients was analysed for possible sequence variations in the ALD gene by PCR amplification and single strand conformation polymorphism analysis. Three missense mutations (Ser515Phe, Glu267Lys and Arg401Trp) and a 9-bp deletion were detected predicting, respectively, the replacement and absence of amino acids in the deduced amino acid sequence of the ALD protein. In the patients' families, detection of the respective mutations allows the identification of carriers of ALD/AMN. Mutational screening in ALD families is of practical importance in improving genetic counseling.

Distribution of apolipoprotein E genotypes in Asian Indians, Hungarians, and Papua New Guineans.

We report here the distribution of apo E genotypes and allele frequencies in Asian Indians, Hungarians, and Papua New Guineans using the DNA based analysis. Frequency of the apo E4 allele was thrice as high in Papua New Guineans as compared to the Caucasians. The rare apo E2 allele was also present in higher frequency in the Papuas as compared to other populations.

Serum protein and erythrocyte enzyme polymorphisms in twelve population groups of Hungary.

The distribution of the serum proteins C3, TF, HP, GC, BF, AMY2, PLG, GM, and KM and the erythrocyte enzyme polymorphisms GLO, GPT, ESD, ACP, 6-PGD, ADA, AK, PGM1 and PGP amongst twelve population groups in Hungary was investigated. Gene frequencies and genetic distances are discussed in relation to the present geographical locations of these groups and their probable history of migration.

Alcohol use, abuse, and alcohol-related disorders among ethnic groups in Hungary. Part I: Csángós from Egyházaskozár Region.

This paper reports the results of a study on alcohol drinking habits, alcohol-related acute symptoms, and alcohol abuse among Csángós, an ethnic minority in Hungary. The demographic data revealed their social characteristics: growing old, low education, endogamous marriages, early maternal age at birth of the first baby, and a high child number per family. Alcohol use survey revealed that alcohol consumption of the Csángós is considerably high; more than half of Csángó males and more than one-quarter of Csángó females are heavy drinkers. While all kinds of alcohol are consumed by males, wine drinking is more common among females. Acute reactions to a moderate dose of alcohol evoked a series of physical and physiological symptoms including facial flushing, higher pulse rate, tachycardia and euphoria among at least one third of the probands. There was a distinct gender difference in response to alcohol drinking. While a higher percentage of females reported intense skin flush (34%), a greater percentage of males reported symptoms such as sleepiness, euphoria and aggressiveness. The distribution of clinical chemical markers of alcohol abuse in the sera of the individuals under study confirmed heavier alcohol consumption among males than among females. Alcohol-related mortality data indicate liver cirrhosis and liver cancer as the leading cause of deaths among Csángó males. A high alcohol consumption among Csángó ethnic group reflects the acceptance of alcohol use in the community as an integral part of their lifestyle.

Alcohol use, abuse, and alcohol-related disorders among ethnic groups in Hungary. Part II: Palócs from Mátraderecske.

An epidemiological study on alcohol drinking habits, alcohol metabolism rate, alcohol-related acute physiological symptoms, and alcohol misuse among Palócs, an ethnic minority in Hungary, was conducted. The demographic and sociocultural correlates revealed their ethnic identity: low to moderate education, relatively low number of children per family and higher percentage of skilled workers among males. Alcohol use survey revealed that frequency of alcohol consumption among Palóc male population is considerably high. While about 41% of the Palóc males reported to drink daily between 30 ml and 90 ml pure alcohol, only 5% of the females reported to consume this amount regularly. 53% of males and less than 1% of females were classified as heavy drinkers (consuming more than 60 ml absolute alcohol per day). While all kinds of alcoholic beverage was reported to be consumed by the males, Pálinka (a kind of brandy) drinking was more common among females. About 45% of the Palócs reported to experience acute reactions after drinking a moderate dose of alcohol. The physical and physiological reactions include facial flushing, higher pulse rate, tachycardia and euphoria. While there was no distinct gender difference in facial flushing response to alcohol drinking, a higher percentage of males (70%) reported symptoms such as sleepiness, euphoria and aggressiveness as compared to about only 36% females reporting such reactions. Distribution of clinical chemical markers, in particular GGT values confirmed a heavier alcohol consumption among males than among females. High GGT value also correlated with a positive alcohol-related facial flushing reaction in males.

Ecogenetic and pharmacogenetic studies in Hungary.

12 population groups of Hungary, 1514 individuals altogether, have been studied for polymorphisms of alpha 1antitrypsin, serum cholinesterase, paraoxonase and delta-aminolevulinic acid dehydrase, N-acetyltransferase variation and aldehyde dehydrogenase deficiency. A possible relationship between their allele frequencies and environmental factors in the context of ecogenetic and pharmacogenetic phenomena in Hungary is discussed.

[Benefits of ecogenetics in Hungary]. / Az ökogenetika magyarországi hasznosítása.

Five enzymes and one protein were studied in 10 ethnical and two reference groups involving 1370 persons. The frequency of atypical heterozygotes of plasma cholinesterase was 2.7%. Aldehyde dehydrogenase I isozyme deficiency was found in four persons including two gypsies. The low paraoxonase activity was found in 48.7% of persons examined. The proportion of gene frequencies of sigma-ALADH-1 and sigma-ALADH-2 in the locus of sigma-amino-levulinic acid dehydratase was 9:1. The percentage of slow acetylators was 56.9% in the total study sample. The rate of heterozygotes in Pi alleles of alpha 1-antitrypsin (protease-inhibitor) was 3.7% and one Pi ZZ phenotype could be observed.

Monomorphism of formaldehyde dehydrogenase in different populations.

Blood samples from Koreans, Chinese, Hungarians and Germans were analyzed by isoelectric focusing on polyacrylamide gels and stained for formaldehyde dehydrogenase (FDH) activity. Three activity bands (one major and two minor) were observed in all blood samples studied. No distinct intra- and interpopulation differences were observed in the intensity of the three bands. Human autopsy liver samples also showed a similar three-activity band profile. An additional cathodic band was detected in a single case of autopsy liver extract from a Chinese subject. An apparent identity of FDH with the class III alcohol dehydrogenase was confirmed.

Red cell enzyme and serum protein polymorphisms in South Korea.

Two population groups in South Korea, one from Kwangju and one from Kangreung, were studied in regard to the erythrocyte enzyme polymorphisms GPT, ACP, GLO, ESD, 6PGD, ADA, AK, PGP and subtypes of PGM1 as well as regarding the serum protein variants of C3, HP, BF, PLG, AMY and the subtypes of GC, TF and PI. The results were compared with data of the population groups from the area of Cheju Island, Taejon and Seoul. The Korean population showed a rather high degree of genetic homogeneity.

Red cell and serum protein polymorphisms in three population groups of South Korea.

Genetic markers ACP1, PGM1 with subtypes, ESD, GLO1, PGD, GPT, PGP, C3, TF and GC with subtypes, BF, HP, AMY, PLG and PI, were studied in three populations in South Korea, one being the population of the industrial capital Seoul, the second a rural group from Taejon and the third the population of Cheju Island. For the polymorphic systems studied in the present work, a general similarity was observed among the three populations, with the exception of GPT and ACP1 (Taejon vs. Seoul) and subtypes of GC (Taejon vs. Cheiu).

Genetic markers among three population groups of Hungary.

Three ethnic groups from Hungary, the general population of Hungary, the Matyo and the Gypsies, were examined with respect to the genetic markers PGP, GLO1, GPT, ACP1, ESD, PGD, ADA, AK1, PGM1 subtypes, C3, BF, HP, GC subtypes, PI, TF subtypes and AMY2. Significant variations were noted for the gene frequencies of GPT and PGD between the Hungarian and Matyo sample. The Gypsies deviate in the systems of GLO1, ACP1, ADA, C3, BF and HP from the Hungarians.

Distribution of alpha-1-antitrypsin and haptoglobin phenotypes in bladder cancer patients.

Frequencies of the alpha 1-antitrypsin (Pi) alleles and haptoglobin phenotypes have been determined in a series of 264 North-German patients with bladder cancer. Compared to a healthy control population, we found a statistically significant decrease of Hp 2-2 phenotype in the patient series. A significant increase of the serum Pi Z allele, as previously shown for patient groups with certain other tumours, could also be confirmed for bladder cancer. Furthermore, a distinct association between a lowered M 3 allele and bladder carcinoma was observed.

Polymorphism of 6-PGD in South Korea: a new genetic variant 6-PGD Korea.

During population genetic studies in Korea a new variant in the 6-phosphogluconate (6-PGD) system preliminary called 6-PGDKorea was observed.

delta-Aminolevulinic acid dehydrase (porphobilinogen synthase) in two families with inherited enzyme deficiency.

The inheritance of a deficient delta-aminolevulinic acid dehydrase (ALA-D; synonym: porphobilinogen synthase; EC 4.2.1.24) was studied in blood samples of two families over three generations. The propositus in each family was a young male acute hepatic porphyria patient with an almost complete ALA-D deficiency in the homozygous state (ALA-D activity less than 2% of controls). Heterozygotes are clinically non-affected (mean ALA-D 36% of controls). The mode of transmission could be traced by enzyme activity and electrophoretic polymorphism studies. Heterozygotes are detected by the demonstration of enzyme activity in the gel. The notation D was used for the gene expressing the defective enzyme. The "phenotype" D-1 was observed in six, the "phenotype" D-2 in three of all heterozygotes studied. These results are compatible with a single normal allele in heterozygotes responsible for enzyme activity. Quantitative assays and the segregation pattern in both families suggest a 3-allele-system for the inheritance of ALA-D deficiency.

Polymorphisms of Pi, Hp, ADA and AK in Mongolian, Korean and Zhuang populations of China.

Three minority ethnic groups from China, Mongolian, Koreans, and Zhuangs were studied for the genetic markers AK, ADA, Hp, and Pi. AK was monomorphic in Koreans and Zhuangs. Significant differences were observed in the Hp system between Mongolians and Zhuangs.

Genetic studies in Atacameño Indians: serum protein and red cell-enzyme polymorphisms.

Phenotype and gene frequencies among Atacameño Indians are presented for nine serum protein polymorphisms (Hp, Gc with subtypes, Tf with subtypes, Amy, C3, Bf, PLG) and nine red-cell-enzyme polymorphisms (AcP, PGM1 with subtypes, AK, ADA, 6-PGD, GPT, EsD, GLO). Four systems--Tf, Amy, AK, ADA were found to be monomorphic. In the PGM1 subtypes an extremely high frequency of PGM1a3 could be observed. In two samples a new Gc mutant was identified and classified as Gc1A26. In the EsD system an unusual phenotype was detected in one sample.

Distribution of eight blood-group systems and ABH secretion in Mongolian, Korean, and Zhuang nationalities in China.

Among different blood-group systems investigated here, the distribution of the ABO system varies most of all, followed by MNSs and P. Although there are differences in ABH secretion in the different populations, no striking regularity has been found. No significant difference has been found in the distribution of the blood-group systems Rhesus, Diego, Duffy, Kell and Kidd in these Chinese populations: the Rh (-) rate is less than 1%, the frequency of Dia is about 0.04, the frequency of Fya is rather high, the frequency of K extremely low and Jka is about 0.4. In the three nationalities under study, Mongolians are characterized by a high frequency of IB, M higher than 0.5 and a relatively high frequency of P1. Koreans are characterized by a high frequency of IA, slightly more M than N and rather high CDE in the Rh system. The peculiarities of the Zhuangs are a rather high frequency of IO and M and the lowest frequency of P1.

Population genetic studies in three Chinese minorities.

Three minority ethnic groups from China (Mongolians, Koreans, Zhuang) were examined with respect to the genetic markers GLO, GPT, ACP, ESD, 6-PGD, PGM1 subtypes, C3, and TF. Significant variations were noted for the gene frequencies of GLO, GPT, ESD, sub PGM1 between Zhuang and Mongolians; for GPT, ACP, ESD, sub PGM1 between Zhuang and Koreans; and for GLO between Mongolians and Koreans.