AREDYLD: a syndrome combining an acrorenal field defect, ectodermal dysplasia, lipoatrophic diabetes, and other manifestations.

A daughter of second cousins is described as having lipoatrophic diabetes, unusual facial appearance, generalized hypotrichosis, two natal teeth with enamel dysplasia, eruption of four dysplastic deciduous teeth, absence of permanent dentition, low birth weight, short stature, lumbar scoliosis, renal alterations, aplasia of a breast and hypoplasia of the other, hypoplastic and hypopigmented areolae with diffuse limits, hyperostosis of the cranial vault, metacarpal hypoplasias, difficulty of grasping with the left hand, exertional dyspnea, absence of DIP extension and flexion creases, dermatoglyphic alterations, and other anomalies. Her sister, dead at 1 1/2 years, had had some manifestations of the condition; seven sibs are normal. It is more likely that the whole clinical picture represents a single syndrome rather than homozygosity of different autosomal-recessive genes.

The X-X-/E+E+ genotype of the XbaI/EcoRI polymorphisms of the apolipoprotein B gene as a marker of coronary artery disease in a Brazilian sample.

Studies that consider polymorphisms within the apolipoprotein B (apo B) gene as risk factors for coronary artery disease (CAD) have reported conflicting results. The aim of the present study was to search for associations between two DNA RFLPs (XbaI and EcoRI) of the apo B gene and CAD diagnosed by angiography. In the present study we compared 116 Brazilian patients (92 men) with CAD (CAD+) to 78 control patients (26 men) without ischemia or arterial damage (CAD-). The allele frequencies at the XbaI (X) and EcoRI (E) sites did not differ between groups. The genotype distributions of CAD+ and CAD- patients were different (chi (1) = 6.27, P = 0.012) when assigned to two classes (X-X-/E+E+ and the remaining XbaI/EcoRI genotypes). Multivariate logistic regression analysis showed that individuals with the X-X-/E+E+ genotype presented a 6.1 higher chance of developing CAD than individuals with the other XbaI/EcoRI genotypes, independently of the other risk factors considered (sex, tobacco consumption, total cholesterol, hypertension, and triglycerides). We conclude that the X-X-/E+E genotype may be in linkage disequilibrium with an unknown variation in the apo B gene or with a variation in another gene that affects the risk of CAD.

Probable assignment of the serum cholinesterase (E1) and transferrin (Tf) loci to chromosome 1 in man.

Suggestions of linkage in males between the E1 and Rh loci (Z = + 1.849; THETA = 0.20) and between the Tf and Rh loci (Z = + 0.595; THETA = 0.35) are presented. The assignment of the E1 and Tf loci to chromosome 1 and the order Tf:E1:PGD:Rh:PGM1 are cautiously proposed.

CHE1 UF serum cholinesterase phenotype in whites and non-whites from southern Brazil as determined by a new method.

A sample of 251 Whites and 818 Non-Whites, from Curitiba (southern Brazil), was typed with a new method with the aim of estimating the frequency of the CHE1*F allele. The frequency of this allele did not differ between Whites (0.60 +/- 0.34%) and Non-Whites (0.49 +/- 0.17%), being estimated as 0.51 +/- 0.15% for the whole sample. The use of the inhibitors DL-propranolol and RO2-0683 with alpha-naphthylacetate as substrate (at 37 degrees C) was efficient for discriminating between the CHE1 U and CHE1 UF phenotypes.

Butyrylcholinesterase variants (BCHE and CHE2 Loci) associated with erythrocyte acetylcholinesterase inhibition in farmers exposed to pesticides.

Farmers exposed to pesticides and classified as mildly poisoned and controls on the basis of erythrocyte acetylcholinesterase (AChE) activity were examined for butyrylcholinesterase (BChE) genetic variability. The mildly poisoned group showed a significantly higher frequency of non-usual phenotypes (13.1%) than the control group (1.7%). These phenotypes showed a relative risk (RR) of 8.8 of erythrocyte AChE inhibition when compared to the usual phenotype. Among the subjects with the usual phenotype, the CHF2 C5- phenotype was more frequent in the mildly poisoned group (94.3%) than in the control group (81.0%), leading to an RR of 3.9 when compared to the CHE2 C5+ phenotype. When the total sample was classified into two groups (usual CHE2 C5+ and other phenotypes), the usual CHE2 C5+ phenotype was found to be responsible for a preventive fraction of about 14% of the cases of mild poisoning. The present data suggest that BChE genetic variability offers differential protection against erythrocyte AChE inhibition.

Association of the CHE2 locus with body mass index and butyrylcholinesterase activity.

The butyrylcholinesterase (BChE; EC 3.1.1.8) activities of two electrophoretic bands of the CHE2 C5+ phenotype--C5 and C(OF) (other forms)--were quantified by densitometry in 100 individuals. The activity data suggested that, in addition to determining C5, the CHE2*C5+ allele also increases the level of other BChE forms. Since the relative activity of C5 showed the highest correlation coefficient with weight when compared with the other BChE activity variables (total, absolute C5, and absolute C(OF)), its median activity level was used for the classification of CHE2 C5+ phenotypes (faint and intense). Mean body mass index (BMI) was compared among the CHE2 locus phenotypes-controlled by sex, age, and ethnic group. It was shown that the intense CHE2 C5+ phenotype presents a significantly lower (p < 0.001) mean BMI (23.2) than the other phenotypes (faint CHE2 C5+ = 25.2; CHE2 C5- = 25.4). It seems that the relative COF activity is positively associated with fat storage, since CHE2 C5- and faint CHE2 C5+ phenotypes showed higher mean BMI than the intense CHE2 C5+ phenotype. Our hypothesis is that the presence of C5 in a relatively high proportion leads to less fat storage.

Frequency of the CHE1*K allele of serum cholinesterase in a sample from southern Brazil.

The frequency of the CHE1*K allele was estimated as 2.04 +/- 2.02% in a population sample from Southern Brazil. Previously reported estimates refer to the British population and are significantly higher than the present one. Our hypothesis is that the British frequencies may represent overestimates due to ascertainment conditions.

Frequencies of atypical serum cholinesterase in a mixed population of northeastern Brazil.

Frequencies of the CHE1*A allele were estimated in 84 Whites and 772 Negroids from a random sample of Salvador, Bahia. The overall frequency of this gene in Negroids was estimated as 0.842 +/- 0.233%. This indicates that this sample presents around 50 +/- 17% of White admixture and that the estimate of the risk of developing prolonged apnoea in individuals submitted to suxamethonium is around 0.035%, that is about 1 out of 2,900.

Frequencies of atypical serum cholinesterase among Caucasians and Negroes from southern Brazil.

Frequencies of the CHE1*A allele were estimated on the basis of a sample of 999 Caucasians (1.5%) and 1,015 Negroids (0.84%) from Curitiba, Brazil. The frequency found in the Negroid subsample allows an estimate of 50 +/- 15% of Caucasoid admixture and an average gene flow in the white-black direction of the order of 5.6% per generation.

Butyrylcholinesterase and obesity in individuals with the CHE2 C5+ and CHE2 C5- phenotypes.

OBJECTIVE: To investigate the association between butyrylcholinesterase (BChE) activities (total and band specific) and body mass index (BMI) in obese and nonobese individuals, considering other variables (anthropometric, biochemical and hormonal) and the leanness process. SUBJECTS: Obese (BMI> or =30 kg/m(2); N=181) and nonobese individuals (N=265), classified according to the CHE2 locus phenotypes, with the obese patients being followed-up when submitted to a weight-loss program. MEASUREMENTS: Anthropometric (weight, height, BMI, waist, waist/hip ratio-WHR, triceps and subscapular skinfolds, percentage of body fat and arterial pressures), hormonal (insulin, estradiol-E(2), triiodothyronine-T(3) and thyroxine-T(4)) and biochemical (glucose, total cholesterol, HDL-C, triglycerides, uric acid, urea, creatinine, sodium, potassium and BChE activities) variables. RESULTS: Although obese CHE2 C5- individuals presented higher mean BChE activities than their CHE2 C5- controls and diminished mean activities with leanness, similar comparisons did not show any difference in the CHE2 C5+ group. Furthermore, the mean serum potassium values of obese individuals were significantly higher in the CHE2 C5+ than in the CHE2 C5- phenotype. The BChE activities were less related to BMI in obese CHE2 C5- individuals than in their controls. In the CHE2 C5- obese group, significant regression coefficients were found between BChE activity variables and BMI (+), ethnic origin (higher in Euro-Brazilians), sex (higher in males), diastolic pressure (-), triceps skinfold (+), total cholesterol (+), T(3) (+) and E(2) (-). The main findings in the CHE2 C5+ obese group: mean insulin levels decreased with leanness and a significant correlation was detected between the C(5) complex activity and creatinine (+), insulin (-) and WHR (-); a significantly higher frequency of weight loss occurred compared to the CHE2 C5- group. CONCLUSION: In the present study, different relations between obesity and some of the studied variables were found when CHE2 C5+ and CHE2 C5- individuals were compared.

The C5 isozyme of serum cholinesterase and adult weight.

The relationship between the CHE2 locus of serum cholinesterase (BChE) and adult human weight was studied in a sample of 225 CHE2 C5+ individuals and 225 CHE2 C5- controls matched for sex, height, age and race. With respect to the intensity of the C5 band staining (scored 1-6), 113 individuals had faint C5 bands (scores 1-3) and 112 intense C5 bands (scores 4-6). The individuals with intense CHE2 C5+ phenotype showed a significantly lower mean adult weight (64.66 +/- 0.73 kg) when compared to their controls (70.59 +/- 0.97 kg) and a significant reduction in weight variance (59.81 and 105.18, respectively). Individuals with faint C5 bands, although showing a negative correlation between weight and C5 band intensity, did not differ from their controls in mean weight.

An improved method for butyrylcholinesterase phenotyping.

An improved method for the identification of butyrylcholinesterase phenotypes is proposed. It is based on modifications of a method that uses alpha-naphthyl acetate as substrate and DL-propranolol and Ro2-0683 as inhibitors. The proposed modifications make the method more rapid and increase the accuracy of the determinations of the phenotypes tested (BCHE U, BCHE UF, BCHE UA, BCHE AK, BCHE AF, and BCHE A). These modifications make the method even more adequate for population studies and clinical routine.

Frequencies of the butyrylcholinesterase K mutation in Brazilian populations of European and African origin.

The frequency of the butyrylcholinesterase K mutation was calculated on the basis of data obtained by polymerase chain reaction primer-introduced restriction analysis (PCR-PIRA). The population sample was composed of 177 Brazilians: 95 whites of predominantly European ancestry and 82 admixed individuals (European and African origin). The frequencies--18.4 +/- 2.8% for whites and 17.1 +/- 2.9% for admixed--did not differ from those previously obtained in North America, Scotland, Japan, and Denmark. The occurrence of the K mutation in Europeans, East Asians, and Africans suggests a relatively old origin for this mutation, and the similar frequencies found in these populations may suggest the operation of selective forces.

Butyrylcholinesterase activity and risk factors for coronary artery disease.

The aim of this study was to verify which risk factors for coronary artery disease (CAD) are independently correlated with butyrylcholinesterase (BChE) activity. We studied 88 White individuals (43 males) aged 47.3+/-15.7 years (mean+/-SD; range: 14.0-80.0 years) including 38 with hyperlipidemia, 30 with hypertension and 5 with diabetes mellitus (DM). Simple correlation analysis showed that BChE activity was positively correlated with age, sex, body mass index, hypertension and DM, as well as with triglycerides (TGs), total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B (Apo B). However, after a step-wise multiple regression analysis, the only risk factors for CAD that showed independent correlations with BChE activity were, in descending order of importance, Apo B, TGs and DM. Our findings seem to reinforce suggested associations of BChE activity with lipoprotein synthesis and with hypertension, as well as supporting previous data on the relation of BChE activity with disturbances found in diabetes mellitus.

Studies on a heterologous complex formed by human butyrylcholinesterase.

An electrophoretic band with butyrylcholinesterase activity was detected in 71 CHE2 C5+ and 378 CHE2 C5- individuals and was named C4/5 in view of its similar mobility to either C4 or C5, depending on the pH of the agar gel used. The present data suggest that C4/5 is a heterologous complex of butyrylcholinesterase. Although the C4/5 band may have the same mobility as C5, depending on the conditions of electrophoresis, our hypothesis is that these two bands result from the association of BChE with different molecules.

Butyrylcholinesterase polymorphisms (BCHE and CHE2 loci) in Brazilian Indian and admixed populations.

The genetic variability of butyrylcholinesterase, determined by the BCHE and CHE2 loci, was examined in nine Brazilian Indian groups. In addition, a search for the presence of the BCHE*F allele was also performed in eight other Brazilian Indian samples and in five admixed (black-Indian-white) rural Amazonian communities previously studied for the CHE2 locus and the BCHE*A allele. In the Indian populations the frequency of the BCHE*F allele varied from 0 to 7.1% +/- 3.4 and the frequency of the CHE2 C5+ phenotype ranged from 1.4% +/- 1.4 to 45.9% +/- 3.8. This study seems to be the first to report the presence of the BCHE*F allele in native Americans. The BCHE*A allele appeared in one Indian group (1.4% +/- 1.0), and we suggest that its existence in this tribe and in other native Americans can be explained by gene flow from white populations. Gene flow may also be the reason for the occurrence of the BCHE*F allele in Brazilian Indians, whereas the CHE2*C5+ allele may have been present in the paleo-Indians. The distributions of both the BCHE*F allele and the CHE2 C5+ phenotype in Brazilian Indians seem to be the result of the action of random genetic drift.