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B K Suarez

Publications and source records attributed to B K Suarez.

At least 37 records · Page 2Linked to original sources
PubMed1995

Monoamine oxidases and alcoholism. I. Studies in unrelated alcoholics and normal controls.

Low platelet MAO activity has been associated with alcoholism. In order to evaluate the role of MAO genes in susceptibility to alcoholism, we have taken a biochemical and molecular genetic approach. The sample consisted of 133 alcoholic probands who were classified by subtypes of alcoholism and 92 normal controls. For those subjects typed for platelet MAO activity, alcoholics (N = 74) were found not to differ from the non-alcoholics controls (N = 34). Neither was there a significant difference between type I and type II alcoholics or between either subtype and normal controls. However, we do find significant differences between male and female alcoholics, but not between male and female controls. The allele frequency distribution for the MAO-A and MAO-B dinucleotide repeats is different between the alcoholic sample (N = 133) and the normal control sample (N = 92). In a two-way analysis of variance of MAO-B activity as a function of the allelic variation of each marker locus and diagnosis, there is no evidence for mean differences in activity levels for the different alleles. Our findings do not rule out a role for the MAO-B gene in controlling the enzyme activity because the dinucleotide repeats are located in introns.

Adult↗
PubMed1995

Monoamine oxidases and alcoholism. II. Studies in alcoholic families.

Thirty-five alcoholic families have been studied to investigate the relationship between DNA markers at the monoamine oxidase (MAO) loci and 1) platelet activity levels and 2) alcoholism. A quantitative linkage analysis failed to reveal any evidence that the variation in activity levels cosegregates with the DNA markers. A sib-pair analysis did not reveal a significant excess of MAO haplotype sharing among alcoholic sibs, although the deviation from random sharing was in the direction consistent with an X-linked component. A reanalysis of platelet MAO activity levels in a subset of these families revealed that the lower levels previously found in alcoholics is more likely due to the differences between males and females. Only among males and only when a "broad" definition of alcoholism is used (and MAO activity levels are transformed to normality) does it appear that alcoholics have depressed activities compared to nonalcoholics. Finally, when the confounding due to gender difference is removed, no differences between type I and type II alcoholics are found in these families.

Alcoholism↗
PubMed1995

Sib-based detection of QTLs.

Association and transmission/nontransmission analyses were used in a split sample design to identify disease susceptibility alleles at two loci. Sib-pair analysis on various subsets of the data identified an additional four regions that yielded signals of disease predisposing quantitative trait loci (QTLs). Three of these four regions represented Type I errors. A new simulation indicates that a multiplex sampling strategy would substantially improve QTL detection for this oligogenic transmission model.

Alleles↗
PubMed1995

A chromosome-based method to infer IBD scores for missing and ambiguous markers.

We propose a probability model to impute missing identical-by-descent (IBD) vectors for linkage analysis, when adjacent marker loci are typed and interference is estimable. A chromosome-based IBD distribution, conditioned on available marker data, is computed using a fast algorithm to estimate the joint probability of genes IBD at several equally spaced linked loci. Weighted IBD vectors are then used in various test statistics for linkage analysis. As an example, we analyzed the 18 affected sib pairs in the GAW9 Problem 1 data set using Risch's lod-score test.

Algorithms↗
PubMed1995

Familial aspects of prostate cancer: a case control study.

PURPOSE: We evaluated the importance of positive family history, age at diagnosis and history of vasectomy in predicting the risk for prostate cancer in the brothers of prostate cancer patients. MATERIALS AND METHODS: A total of 1,084 men with newly diagnosed prostate cancer responded by interview to a family history survey, which included detailed information on the diagnosis of any cancer in the parents of the proband, diagnosis of prostate cancer in male relatives and age at onset of prostate cancer in the proband. A history of vasectomy was also obtained from the proband. The control cases consisted of 935 spouses of the probands who were administered the same questionnaire in an identical fashion. RESULTS: Prostate cancer was not significantly associated with other types of cancer in proband parents. The presence of prostate cancer in the father, grandfather or uncle of the proband significantly increased the risk of prostate cancer in proband brothers. Early age at onset in the proband was also associated with an increased risk to the proband brothers. CONCLUSIONS: Men with a family history of prostate cancer are at a significantly increased risk for prostate cancer, especially if the affected relative had early onset of cancer. Prostate cancer does not seem to be associated with a higher incidence of other cancers in family members.

Adult↗
PubMed1994

Linkage disequilibria at the D2 dopamine receptor locus (DRD2) in alcoholics and controls.

Because of its central role in the neuromodulation of appetitive behaviors, the D2 dopamine receptor gene (DRD2) has received considerable scrutiny as a possible candidate that may affect susceptibility to additive behaviors--especially alcoholism. Association studies that compare the frequencies of anonymous restriction fragment length polymorphisms (RFLPs) in alcoholics and controls have yielded equivocal results, suggesting that any role played by this receptor will account for only part of the variation. Since these RFLPs are not located in coding regions, the hypothesis has been advanced that the association seen in some studies results from linkage disequilibrium between these markers and one or more functional DRD2 alleles that affect susceptibility. To test this hypothesis, we have assayed four DRD2 RFLPs that span coding regions as well as a 3' flanking RFLP in an expanded sample of 88 unrelated Caucasian alcoholics and 89 unrelated race-matched controls. No significant difference for any RFLP frequency between these samples was observed, although for one marker (phD2-244), the alcoholic sample showed a significant departure from the Hardy-Weinberg equilibrium. The pattern of pairwise composite disequilibrium coefficients is broadly similar in the two samples, although when the five-marker haplotype frequencies are compared, a significant difference is revealed. This difference appears to be due to greater linkage disequilibrium of the control sample. These results do not support the involvement of the DRD2 region in the etiology of alcoholism.

Adult↗
PubMed1994

Monoamine oxidases and alcoholism: studies in unrelated alcoholics, normal controls and alcoholic families.

Monoamine oxidases (A and B) are of great interest in connection with alcoholism. Low MAO activity has been found in the brains and the platelets of alcoholics and their relatives supporting the hypothesis that low MAO activity is a biological marker for vulnerability to misuse. In order to determine the role of the MAO genes in alcoholism we have measured MAO-B activity and typed two simple sequence repeats (one in the MAO-A gene and one in the MAO-B gene) in a sample of 133 unrelated alcoholics, 300 subjects from 30 two- and three-generation pedigrees ascertained through an alcoholic proband, and 92 normal controls. The unrelated alcoholic group did not differ in MAO-B activity from normal controls nor were there significant differences between subtypes. We did, however, find significant differences between alcoholic males and females (t = 2.836, p = .005), a difference that was not present in controls. A two-way analysis of variance of MAO-B activity as a function of the allelic variation of each marker locus and diagnosis among male subjects was performed. There was no evidence for mean differences in activity levels for different alleles. The distribution of MAO-A and MAO-B "alleles" in the alcoholic sample differed from that of the control sample. Affected sib pair linkage analysis of MAO genes and alcoholism showed no evidence for an excess of concordant affected sib pairs suggesting that this region of the X-chromosome does not harbor a susceptibility locus.

Adult↗
PubMed1993

Alzheimer's disease: a piscatorial trek.

The evidence for linkage between Alzheimer's disease and markers on both chromosomes 19 and 21 [Pericak-Vance et al., 1991] by the affected-pedigree-member (APM) method [Weeks and Lange, 1988] cannot be replicated on any of the available GAW8 data sets when marker allele frequencies are estimated from the combined sample. The strong dependence of the APM method on accurate estimation of marker allele frequencies, and the effects of noninformative pairs and of genetic distance in informative pairs of relatives are illustrated.

Aged↗
PubMed1992

Patterns of genetic variation in Native America.

Allele frequencies from seven polymorphic red cell antigen loci (ABO, Rh, MN, S, P, Duffy, and Diego) were examined in 144 Native American populations. Mean genetic distances (Nei's D) and the fixation index FST are approximately equal for the North and South American samples but are reduced in the Central American geographic area. The relationship between genetic distance and geographic distance differs markedly across geographic areas. The correlation between geographic distance and genetic distance for the North and Central American data is twice as large as that observed for the South American samples. This geographic difference is confirmed in spatial autocorrelation analyses; no geographic structure is apparent in the South American data but geographic structure is prominent in North and Central American samples. These results confirm earlier observations regarding differences between North and South American gene frequency patterns.

Blood Group Antigens↗
PubMed1991

Alcoholism and alleles of the human D2 dopamine receptor locus. Studies of association and linkage.

The association of the A1 allele of the D2 dopamine receptor gene with alcoholism was examined by comparing 32 unrelated white alcoholics with 25 unrelated white controls and by analysis of 17 nuclear families in multigenerational pedigrees of alcoholics in whom the A1 allele was segregating. All subjects had structured psychiatric interviews. Clinical assessment and genotyping were carried out independently. Thirteen (41%) of the 32 alcoholics carried the A1 allele compared with three (12%) of the 25 controls. The association with the A1 allele was significant when controls were compared with a subset of 10 alcoholics with severe medical problems (60% vs 12%), but not less severe cases. However, regardless of clinical severity or subtype, there was no evidence of linkage or cosegregation of the A1 allele and increased susceptibility to alcoholism in informative pedigrees. The possible association in the general population without linkage in families may be explained either by chance variation in our small samples or a modifying effect of the A1 allele that increases severity. Further study of the role of the D2 receptor gene in alcoholism is warranted.

Alcoholism↗
PubMed1988

Genes associated with the G2m(23) immunoglobulin allotype regulate the IgG subclass responses to Haemophilus influenzae type b polysaccharide vaccine.

We determined whether genes associated with the G2m(23) allotype, a genetic marker on IgG2 molecules, influence the subclass composition of the antibody response to Haemophilus influenzae type b polysaccharide vaccine. After immunizing 70 white adults, the geometric means (GMs) of the total, IgG, IgG1, and IgG2 antibody concentrations increased approximately 10-fold over preimmunization concentrations. There was no significant difference in the GMs of the total, IgG, or IgG1 antibody concentrations in postimmunization sera from subjects positive versus those negative for G2m(23). Adults positive for G2m(23) had a GM IgG2 concentration more than threefold higher than that of negative subjects (P less than .001). The antibody responses of 61 Amish adults immunized with type b polysaccharide vaccine were also analyzed. Those adults positive for G2m(23) had a higher GM serum IgG2 response to capsule than did those who were negative (P less than .01). These data indicate that genes associated with the G2m(23) locus regulate the IgG subclass composition of the antibody response to H. influenzae type b polysaccharide vaccine.

Adolescent↗
PubMed1986

Hemophilus influenzae type B disease in children vaccinated with type B polysaccharide vaccine.

We studied 55 cases of invasive Hemophilus influenzae type b disease occurring in children at least three weeks after vaccination with type b polysaccharide vaccine. Their mean age at the time of immunization was 27.8 months (range, 18 to 47). Meningitis developed in 39 patients, of whom 3 died and 6 had neurologic sequelae. We investigated certain host factors that may have contributed to the failure of the vaccine. The geometric mean concentration of antibody to type b polysaccharide in convalescent-phase serum from 31 of the vaccinated patients who had hemophilus disease was significantly lower than that in serum from 25 patients of similar age with the disease who had never been vaccinated (0.59 vs. 3.46 micrograms per milliliter, P less than 0.001). However, only 3 of 46 patients in whom the vaccine failed and who were tested for hypogammaglobulinemia had this finding, and none of 33 children tested for IgG2 had low serum concentrations of this immunoglobulin subclass, which is thought to be important in the immune response to polysaccharide antigens. In addition, all but 1 of the 46 patients in whom the vaccine failed and who were tested for IgG antibody to tetanus toxoid protein, a thymic-dependent antigen, had normal values, and 19 of 20 tested for hemolytic complement activity had normal levels. In white children, the presence of the Gm immunoglobulin phenotype (1,2,3, 17; ;5,13,21) was associated with a sevenfold increase in the relative risk of vaccine failure (P less than 0.003). We conclude that vaccine failure may be related in part to genetic factors, and that most vaccinated children in whom Hemophilus influenzae disease develops have deficient antibody responses to the type b polysaccharide despite normal serum concentrations of immunoglobulin and normal antibody responses to tetanus toxoid.

Antibodies, Bacterial↗
PubMed1986

Haemophilus influenzae type b disease in an Amish population: studies of the effects of genetic factors, immunization, and rifampin prophylaxis on the course of an outbreak.

In 1982, an outbreak of Haemophilus influenzae type b disease occurred in a 379-member Amish community. In an attempt to control the outbreak after the occurrence of the second case of disease, we investigated the combination of (1) rifampin chemoprophylaxis of all carriers of H influenzae type b and their household contacts from 1 month to 5 years of age and (2) H influenzae type b polysaccharide vaccine immunoprophylaxis of all community members 12 months of age and older. Despite our intervention, two additional cases of bacteremic H influenzae type b disease occurred in the ensuing 5 months, one in a 22-month-old infant who had been immunized at 19 months of age and the other in a child who had not been immunized because she was younger than 12 months of age. The outbreak ended following rifampin prophylaxis of all community members younger than 15 years of age. All of the children with disease were genetically related to one another, and three of the four were inbred. However, analysis of their coancestry revealed that neither the average level of kinship nor the average inbreeding level of the affected children differed significantly from those of the other children in the community. Furthermore, none of the four children with disease shared a human leukocyte antigen haplotype. Our observations suggest that inbreeding was not a risk factor in this community.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Genetic variation in North Amerindian populations: the geography of gene frequencies.

Ten-level synthetic gene frequency maps derived from a principal component analysis of seven polymorphic loci are displayed for a large sample of North Amerindian populations. These maps are useful for assessing population affinities over broad geographical regions and perhaps, as others have argued, for inferring recent migrations. The influence of European admixture is investigated by deleting highly admixed populations and regenerating the maps. In broad outline the resultant geographic patterning, while appearing more homogeneous, preserves many features of the maps that include the highly admixed samples--especially with respect to the Eskimo/non-Eskimo dichotomy. Further, in an effort to evaluate how varying the number of display levels affects patterning as well as interpretation, the maps were replotted at 5 and 20 levels. The 5-level maps are found to accentuate differences between the full data set and the less admixed data set, while the 20-level maps tend to obscure these differences.

Gene Frequency↗