Analysis of the Fragile X Trinucleotide Repeat in Basques: Association of Premutation and Intermediate Sizes, Anchoring AGGs and Linked Microsatellites with Unstable Alleles.

Fragile X Syndrome (FXS) is associated with an unstable CGG repeat sequence in the 5' untranslated region in the first exon of the FMR1 gene which resides at chromosome position Xq27.3 and is coincident with the fragile site FRAXA. The CGG sequence is polymorphic with respect to size and purity of the repeat. Interpopulation variation in the polymorphism of the FMR1 gene and consequently, in the predisposition to FXS due to the prevalence of certain unstable alleles has been observed. Spanish Basque population is distributed among narrow valleys in northeastern Spain with little migration between them until recently. This characteristic may have had an effect on allelic frequency distributions. We had previously reported preliminary data on the existence of FMR1 allele differences between two Basque valleys (Markina and Arratia). In the present work we extended the study to Uribe, Gernika, Durango, Goierri and Larraun, another five isolated valleys enclosing the whole area within the Spanish Basque region. We analyzed the prevalence of FMR1 premutated and intermediate/grey zone alleles. With the aim to complete the previous investigation about the stability of the Fragile X CGG repeat in Basque valleys, we also analyzed the existence of potentially unstable alleles, not only in relation with size and purity of CGG repeat but also in relation with DXS548 and FRAXAC1 haplotypes implicated in repeat instability. The data show that differences in allele frequencies as well as in the distribution of the mutational pathways previously identified are present among Basques. The data also suggest that compared with the analyzed Basque valleys, Gernika had increased frequency of susceptibility to instability alleles, although the prevalence of premutation and intermediate/grey zone alleles in all the analyzed valleys was lower than that reported in Caucasian populations.

[Prevalence of Barrett's esophagus in patients with colorectal carcinoma]. / Prevalencia de esófago de Barrett en pacientes con carcinoma colorrectal.

OBJECTIVE: To determine Barrett's esophagus (BO) prevalence in patients diagnosed with colorectal carcinoma (CC) and feasibility-associated factors in a 10 week period from March 1st to June 15, 1999. PLACE: Endoscopy Department, Oncology Hospital, Centro Médico Nacional Siglo XXI, IMSS. METHOD: A prospective, transversal, observational and comparative assay of 48 patients with histologically confirmed diagnosis of colorectal carcinoma in whom high endoscopy with biopsy harvest was performed; otherwise, colonoscopy was performed in eight patients with confirmed BO. RESULTS: Thirty men and 18 women were studied with an average age of 53 years of age. In 100%, colon cancer was determined as adenocarcinoma and location were rectal in 43.7%. Prevalence of BO was 22.9% in addition to 0.74 to 2% in the general population. This implies an odds ratio calculated at 36.43 (p = 0.00000) and 3.09 p = 0.00007), respectively, for risk to present BO concomitant with CC. There was no statistical significance in relation to age, smoking habit, and/or alcoholism. Among eight patients with BO without CCR, only one had a tubulovellous polypus (12.5%) identified. CONCLUSIONS: Although the results were not to conclusive to affirm the association of BA with CCR, the high prevalence found justifies the performance of routine endoscopy in CCR carrier patients with reflux symptoms.

Study of a trimeric tandem repeat locus (SBMA) in the Basque population: comparison with other populations.

Microsatellites can be highly unstable and show a high level of polymorphism between individuals. Here we present the analysis of the CAG trinucleotide repeat polymorphism at the SBMA locus in 57 phenotypically normal individuals rigorously assigned to the Spanish Basque population. Results are compared with 100 Spanish non-Basque individuals who were already analyzed by us (175 alleles). This is the first study undertaken in these populations for this marker. In addition, we compared our results with those published for other populations. Relative allele frequencies showed differences between the samples and no unimodal distribution. The expected heterozygosity in the Basque sample was slightly lower than in the non-Basque sample. Conformity with Hardy-Weinberg equilibrium was verified by three tests. When compared with published data, the predominant alleles appear to be the same in the various populations. There are more differences between Basques and other Caucasoid samples than between non-Basques and Caucasoid samples. Population relationships were also examined by dendrograms based on genetic distances. The results obtained showed some peculiarities in the Basque population. The high degree of similarity with other dendrograms based on different markers and the efficiency of this STR marker in differentiating closely related populations, support the potential usefulness of microsatellites as tools for human population studies.

Cytogenetics of autosomal fragile sites: A Basque population study.

Population cytogenetic data on autosomal fragile sites show differences among different ethnic groups. The Basques are an ancient population; their origin is not exactly known and many studies using several traits have shown peculiarities in the Basques. This is the first study about the incidence of autosomal fragile sites in a healthy Basque sample. The results show interindividual variability, no sex differences at a global level, but differences for some fragile sites. Compared with other populations, a higher incidence of rare autosomal fragile sites has been demonstrated (8%). © 1996 Wiley-Liss, Inc.

a-b ridge count in a Basque population: fluctuating asymmetry and comparison with other populations.

We have analyzed the a-b ridge count and its fluctuating asymmetry in a sample (331 males and 290 females) from the Basque region of Alava province, Spain. Significant bimanual differences in the a-b ridge count are apparent only for females, and the sexual differences are significant for both hands. A comparison of the results in the Alava Basque population with results for other Basque populations showed sexual dimorphism. The results for fluctuating asymmetry do not support the hypothesis that if the regression of fluctuating asymmetry on the right and left hands is quadratic, the fluctuating asymmetry is a result of developmental homeostasis. Our data seem to indicate also that the factors that determine the a-b ridge count are canalized in females and males in the same way.

Physical activity as a risk factor for osteoarthritis of the knee.

A case-control study was conducted to evaluate the association between knee osteoarthritis (OA) and physical activity (PA) among a community group aged 40 years and older. Case patients (85 males, 154 females) had radiologically confirmed knee OA with grade 2+ changes, according to Kellgren and Lawrence criteria. Control subjects (85 males, 154 females) had no radiologic evidence of knee OA. A statistically significant positive association between high PA level and knee OA was observed for women, with an age-adjusted odds ratio (OR) of 1.66 and 95% confidence interval (CI) of 1.01 to 2.72. In men no association was observed (OR = 0.95; 95% CI, 0.49 to 1.83). These associations persisted when controlling simultaneously for potential confounders including age, obesity, history of knee injury, and socioeconomic status, indicating that the OA-PA association is limited to women. One possible explanation is that risk factors for knee OA are influenced by hormones.

Fluctuating dermatoglyphic asymmetry: genetic and prenatal influences.

Genetic and environmental prenatal factors influencing the fluctuating asymmetry of the a-b interdigital ridge count are examined. From the results obtained we can conclude that fluctuating asymmetry of the a-b interdigital ridge count is poorly influenced by genetic factors. We suggest that fluctuating asymmetry of dermatoglyphics provides a good measure of developmental stability in humans, especially for males. The results also indicate that random environmental factors, acting before the 19th week of embryonic development, could be related to the differential timing of maturation of the sexes.

Genetic and dermatoglyphic distances among Basque Valleys.

Palmar dermatoglyphics of a sample including 552 males and 701 females from 8 Basque valleys were analyzed. We studied the frequency of palmar pattern types and compared them using correspondence the frequency of palmar pattern types and compared them using correspondence analysis. The results of this comparative study show that there is diversity among valleys and also that this diversity depends on the trait and on sex. Genetic drift could explain this variability found in the Basque population.

Prevalence and mortality rate of congestive heart failure in the United States.

OBJECTIVES: The study was designed to determine the prevalence and mortality rate of congestive heart failure in noninstitutionalized men and women in the U.S. BACKGROUND: Congestive heart failure is a serious condition with significant morbidity and mortality. Earlier epidemiologic descriptions of congestive heart failure were constructed from small surveys, limited data, hospital records or death certificates. No nationally representative data from noninstitutionalized persons have been examined. METHODS: Data collected from the National Health and Nutrition Examination Survey (NHANES-I, 1971 to 1975) were used to determine the prevalence of heart failure on the basis of both self-reporting and a clinical definition. Mortality data were derived from the NHANES-I Epidemiologic Follow-up Study (1982 to 1986). RESULTS: The prevalence of self-reported congestive heart failure approximates 1.1% of the noninstitutionalized U.S. adult population; the prevalence of congestive heart failure based on clinical criteria is 2%. These estimates suggest that between 1 and 2 million adults are affected. Mortality at 10 and 15 years for those persons with congestive heart failure increases in graded fashion with advancing age, with men more likely to die than women. In the group greater than or equal to 55 years old, the 15-year total mortality rate was 39.1% for women and 71.8% for men. CONCLUSIONS: Congestive heart failure is a common problem in the U.S., with significant prevalence and mortality, both of which increase with advancing age. As the population of the U.S. becomes older, the health care impact of congestive heart failure will probably grow.

Effects of genetic and environmental factors on the a-b, b-c and c-d interdigital ridge counts.

A study of 100 MZ (55 female and 45 male) and 97 DZ (50 male and 47 female) same-sexed twin pairs was carried out to analyse the genetic component of the variance of the a-b, b-c and c-d interdigital ridge counts by means of the Christian method. Especially for the a-b interdigital ridge count, we found it important to analyse both sexes separately. Our results suggest that the a-b count in males seems to be more influenced by environmental factors than the other counts. For females, the three interdigital counts seem to have a strong genetic component influencing their phenotypic expression. Factor analysis with VARIMAX rotation showed each interdigital ridge count to be genetically independent.

Characterization of digital dermatoglyphic features in Salazar Valley: comparison with other Basque valleys.

Digital dermatoglyphics of a sample from the Basque Valley of Salazar, situated in the West of the Pyrenees, were analysed. The results showed bimanual differences in both sexes, and also sexual differences for both hands. The comparative study with other Basque valleys showed that, in spite of their supposed common origin, the geographic barriers and the isolation have generated a genetic/dermatoglyphic and linguistic differentiation.

Fluctuating asymmetry in quantitative dermatoglyphic traits: twins and singletons.

Fluctuating asymmetry for the digital quantitative value was analyzed in a sample of twins (mono and dizygotic) and singletons. The aim was to check if the influence of twinning on the development is expressed in a higher fluctuating asymmetry in twins than in singletons. The results have shown that significant differences exist among the three groups studied, and these differences are fundamentally expressed when the radial and ulnar counts are considered separately.

Twin study of digital dermatoglyphic traits: Investigation of heritability.

Digital patterns of a sample of monozygotic and dizygotic twins were analyzed to obtain heritability values for the four basic types of patterns: arch, tented arch, loops, and whorls. Loops have been separated according to their orientation radial or ulnar. To carry out this study, we used the Holzinger and Clark indices. The results show highest concordances for monozygotic twins except for ulnar loops of the left hand and radial ones of the right hand. Different values of heritability were found for the right and left hands, with finger I having the highest values.

Analysis of digital patterns in the Basque valley of Deba: multivariate comparison with other populations.

Eighty-six females and 79 males from the Basque valley of Deba were analyzed with respect to their digital patterns using correspondence analysis. We found that there was a significant sexual difference for only one type of pattern, tented arch. Also, this population was compared with other Basque valley populations and with other Spanish populations. We found great variability among Basque subpopulations, despite their supposed common origin. Dermatoglyphic distances for some traits can be interpreted as genetic distances because there is high heritability of these traits. The results of the comparison between the Deba valley population and other Spanish populations showed that the Deba population is markedly distant from the other populations.

Quantitative and qualitative finger dermatoglyphics in the Basque Valley of Urola, Spain.

Digital dermatoglyphics of an indigenous sample of 87 males and 101 females from the Urola Valley in the Spanish Basque Country are compared with those from the nine other Basque valleys previously analyzed. In both sexes of the Urola Valley, there is a very high frequency of radial loops; the mean found in this valley extends the range of variation for South European-Mediterranean populations, and it is in the superior limit of all Caucasian populations. There are bimanual and sex differences in the frequencies of whorls and loops. Contrary to what occurs normally in populations, in the Urola Valley the frequency of whorls is higher in females and the quantitative value of digital patterns is lower in males. The results of this study show the existence of heterogeneity among valleys for digital trait frequencies and for finger ridge count, and this heterogeneity is more marked in females.

Dermatoglyphic analysis of autistic basque children.

We have analyzed the digital and palmar dermatoglyphics in a sample of autistic children from the Basque Country. The results have been compared with those from a control sample having the same characteristics relative to the ethnic region. We found significant differences between the digital dermatoglyphics of autistic boys and control boys. Autistic children have a higher frequency of transitional radial loops and a lower frequency of dicentric whorls; also the total finger ridge count (TFRC) and radial count are lower in autistic individuals. There were no significant differences in the girls. In palmar dermatoglyphics, autistic girls have a lower frequency of radial loops in the hypothenar area, and the value of the "atd" angle is higher than in control girls. These differences were significant. The a-b interdigital ridge count is significantly lower in autistic boys. Autistic children of both sexes have a higher frequency of aberrant palmar creases. The results obtained in the present study do not contradict the hypothesis that genetic factors may be important in autism of unknown cause.

Nutritional disorders in HIV disease.

Reviewing the medical literature since 1981 show that patients with acquired immunodeficiency syndrome (AIDS) usually suffer from poor ingestion and absorption, increased excretion of nutrients, metabolic and endocrine abnormalities and immunologic abnormalities which impair nutrition. Human immunodeficiency virus (HIV) and associated opportunistic infections stimulate a broad and complex array of responses which include fever, hypermetabolism, leukocytosis, proteolysis of skeletal muscle, and synthesis, by the liver, of acute-phase reactant proteins and various intracellular enzymes. These responses increase gluconeogenesis and lipogenesis, decrease albumin synthesis, and redistribute and/or sequester various trace elements. Infection-induced depletion of body nutrients serves to weaken host resistance. The deterioration of the nutritional status of these patients is likely to have an important effect on the course of the disease. It is thus evident that comprehensive management of HIV infection must include nutritional evaluation and treatment. When oral nutrition proves to be insufficient to maintain adequate intake, alternative routes must be considered. Selection of an appropriate nutritional support formula requires an evaluation of the absorptive capacity of the gastrointestinal (GI) tract, the length of time required for nutritional repletion, costs, patient acceptance, and feasibility of at-home use. Nutritional support maximizes the ability of the AIDS patient to resist infection, may favor the response to medication by decreasing the incidence of adverse drug reactions, and may prolong the quality and productivity of life.