Genomic screen for loci associated with tobacco usage in Mission Indians

Background  

The prevalence of tobacco usage in Native American adults and adolescents is higher than any other racial or ethnic group, yet biological risk and protective factors underlying tobacco use in this ethnic group remain unknown. A genome scan for loci associated with tobacco use phenotypes was performed with data collected from a community sample of Mission Indians residing in Southwest California.     

Is there a genetic susceptibility locus for Parkinson's disease on chromosome 22q13?

The cytochrome P450 mono-oxygenase gene, CYP2D6 on chromosome 22q13 (ch22q13), has been inconsistently associated with Parkinson's disease. Associations with CYP2D6 have either been absent altogether or have involved more than one polymorphism, many of which have the same metabolic effect on gene expression. We examined the association between CYP2D6 polymorphisms and Parkinson's disease in a case-control study and included 10 polymorphic dinucleotide repeat markers linked to CYP2D6 to determine whether the association was present or due to linkage disequilibrium. There was no association between any polymorphism of CYP2D6 and Parkinson's disease, but two of 10 dinucleotide repeat markers linked to CYP2D6 were associated with the disease. These results provide evidence to suggest that there may be an unidentified locus for susceptibility to Parkinson's disease that is in linkage disequilibrium with dinucleotide repeat markers mapping near CYP2D6 on ch22q13.     

Genomic screen for loci associated with alcohol dependence in Mission Indians.

Alcohol dependence is a leading cause of morbidity and mortality in Native Americans, yet biological factors underlying the disorder in this ethnic group remain elusive. This study's aims were to map susceptibility loci for DSM-III-R alcohol dependence and two narrower alcohol-related phenotypes in Mission Indian families. Each participant gave a blood sample and completed an interview using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) that was used to make alcohol dependence diagnoses and the narrower phenotypes of withdrawal, and drinking severity. Genotypes were determined for a panel 791 microsatellite polymorphisms. Analyses of multipoint variance component LOD scores for the dichotomous DSM-III-R phenotype revealed no peak LOD scores that exceeded 2.0 at any chromosome location. Two chromosomes, 4 and 12, had peak LOD scores that exceeded 2 for the alcohol use severity phenotype and three chromosomes 6, 15, 16 were found to have peaks with LOD scores that exceeded 2 for the withdrawal phenotype. Evidence for linkage to chromosomes 4 and 15, and 16 have been reported previously for alcohol related phenotypes whereas no evidence has as yet been reported for chromosomes 6 and 12. Combined linkage and association analysis suggest that alcohol dehydrogenase 1B gene polymorphisms are partially responsible for the linkage result on chromosome 4 in this population. These results corroborate the importance of several chromosomal regions highlighted in prior segregation studies in alcoholism and further identify new regions of the genome that may be unique to either the restricted phenotypes evaluated or this population of Mission Indians.     

Genetic mapping of "Lubag" (X-linked dystonia-parkinsonism) in a Filipino kindred to the pericentromeric region of the X chromosome.

"Lubag" is an X-linked disorder causing dystonia and parkinsonism that has only been described in families from the Philippines, principally from the island of Panay. We have established linkage between the disease phenotype "lubag" and DNA markers which span the Xp11.22-Xq21.3 region by using a large Filipino family with 8 affected men in three generations. These DNA markers define an interval of about 20 centimorgans in the pericentromeric region of the X chromosome as the most likely site of the disease locus XDPD (X-linked dystonia-parkinsonism). XDPD has a maximum multipoint log likelihood ratio score (Zmax) of about 4.6 over the interval from Xq12 to Xq21.31 (DXS159-DXYS1X). The co-occurrence of dystonia and parkinsonism in lubag and in other known disorders suggests there may be a common pathogenetic mechanism. Identification of the genetic defect in this family may provide an important clue toward understanding the pathogenesis and pathophysiology of both dystonia and parkinsonism.     

Discriminant analysis of factors distinguishing patients with functional dyspepsia from patients with duodenal ulcer

Patients with duodenal ulcer or functional dyspepsia do not differ on dyspeptic symptoms. The aim of the present study was to test the hypothesis that functional dyspepsia and duodenal ulcer are two different diagnostic entities by examining the discriminating power of several anamnestic, biological, and psychosocial variables. Ninety-four patients with duodenal ulcer and 86 patients with functional dyspepsia were included. Anamnestic data, global assessment,Helicobacter pylori status, blood group, Lewis^a+ phenotype, and several measures of psychological distress and somatic complaints were registered. Compared to patients with functional dyspepsia, the duodenal ulcer patients were more often infected byHelicobacter pylori and had their stomach discomfort more often relieved by eating. Compared to patients with duodenal ulcer, patients with functional dyspepsia had higher scores of depression, trait anxiety, general psychopathology and different somatic complaints (called somatization). They were also less satisfied with the health care system, their disorder had a greater negative impact on their quality of life, and their global assessment of own health was poorer. Discriminant analysis including age, smoking,Helicobacter pylori status, global assessment, and somatic complaint classified 86.1% of the patients correctly (77.9% of the patients with functional dyspepsia and 93.6% of the patients with duodenal ulcer). It is concluded that duodenal ulcer and functional dyspepsia are two separate diagnostic entities. Patients with duodenal ulcer are older, smoke more often, and almost all are infected withHelicobacter pylori, while patients with functional dyspepsia are characterized by somatization and a negative assessment of their own health.     

Coronary heart disease attack rate, incidence and mortality 1975-1994 in Goteborg, Sweden

MATERIAL AND METHODS: Data from the Göteborg myocardial infarction register wereused to investigate trends in attack rate, incidence of non-fatalmyocardial infarction and mortality from coronary heart diseasein persons aged 64 and below during the period 1975–1994. RESULTS: Myocardial infarction was defined according to strict criteriawhich remained the same throughout the study period. Attackrate and incidence were 3–5 times higher among men thanwomen. The ratio of recurrent infarcts out of all attacks increasedwith increasing age and was 14%, 20% and 24% for men aged 35–44,45–54, and 55–64, respectively. Corresponding ratesfor women were 8%, 14%, and 22%, respectively. Both attack rateand incidence decreased significantly by 2·1–3·9%per year during the study period for most age groups. The 28-dayfatality rate (hospitalized as well as non-hospitalized cases)tended to decline, but significantly so only in the oldest men.The same was true for 28-day fatality among hospitalized patients.The majority of all coronary heart disease deaths occurred outsidehospital in people unaware they had coronary heart disease.Mortality from coronary heart disease decreased by 2·0–68%per year during the study period. In-hospital treatment of myocardialinfarction with intravenous beta-blockers followed by oral treatment,nitroglycerin and thrombolytics increased during the study period.Coronary surgery and angioplasty were used in less than 5% ofpatients during the study period, but increased substantiallyin 1994. CONCLUSION: Coronary heart disease and mortality in ages below 65 yearsare now decreasing in Sweden. Decreasing short-term mortalityis almost certainly due to more efficient treatment in hospital,but as the majority of coronary heart disease deaths occur outsidehospital and in people unaware they have coronary heart disease,primary prevention is still very important.     

Trends in the prevalence, awareness, treatment and control of hypertension: the WHO MONICA Project.

OBJECTIVE: To describe the secular changes in the prevalence, awareness, treatment and control of hypertension. DESIGN: Two independent cross-sectional population surveys using standardized methods conducted between the early 1980s and mid-1990s. SETTING: Twenty-four geographically defined populations of the WHO MONICA Project. PARTICIPANTS: Randomly selected men and women aged 35-64 years. The total number of participants was 69 907. MAIN OUTCOME MEASURES: Two definitions of hypertension were used: 160/95 mmHg or above and 140/90 mmHg or above for systolic or diastolic blood pressure. Subjects on antihypertensive drug treatment were considered to be hypertensive regardless of their blood pressure. Treated subjects whose measured blood pressure level was less than 160/95 or 140/90 mmHg according to the two definitions, respectively, were considered to be adequately treated. RESULTS: The age-adjusted prevalence of hypertension decreased in most and increased in only a few populations. For both definitions of hypertension, the proportion of hypertensive subjects who were aware of their condition increased in three-quarters of the male populations and in two-thirds of the female populations. Furthermore, the proportion of hypertensive individuals on antihypertensive drug treatment increased in three-quarters of the populations. In the final survey, hypertension tended to be better treated and controlled in women than in men. Nevertheless, a large proportion of patients receiving antihypertensive drug therapy still had inadequately controlled blood pressure levels. CONCLUSION: Although awareness and treatment of hypertension according to the data obtained during the late 1980s to the mid-1990s increased in several populations, the effectiveness of antihypertensive treatment showed the continuing need for improvements.