Apolipoprotein E (apoE) polymorphism is one of the genetic determinants of serum cholesterol values. The apoE epsilon4 allele has been associated with advanced coronary heart disease (CHD) diagnosed by angiography, but the role of the apoE genotype in atherosclerosis has not been confirmed at vessel-wall level, nor is any age-dependent effect of the apoE genotype on the development of CHD known.
The right and left anterior descending coronary arteries (RCA and LAD) and the aorta from 700 male autopsy cases (Helsinki Sudden Death Study) in 1981-1982 and 1991-1992 (average age 53 years, range 33 to 70 years) were stained for fat, and all areas covered with fatty streaks, fibrotic plaques, and complicated lesions were measured. In the RCA and LAD, the apoE genotype was significantly associated with the area of total atherosclerotic lesions in men
The consumption of alcohol during the preceding year before death was investigated in 400 consecutive sudden and unexpected natural and non-natural out-of-hospital deaths in males aged 35-69 years in Helsinki. Information about the consumption of alcohol was obtained by interviewing the next kind or a good friend of the deceased (84.5%), or only from the police protocols (13.3%). In the whole material the consumption of alcohol was as follows; the proportion of teetotallers was 6.8%, that of moderate users 35.0% and that of heavy users/alcoholics 56.0%. In addition, there were few undefined cases (2.3%). In general, the consumption of alcohol was heavy in all categories of deaths. However, it was not so heavy among the deceased with a heart disease as the cause of death (the proportion of heavy users/alcoholics 42.9%) as in the other groups of deceased (63.0-85.4%). The results indicate that the heavy chronic consumption of alcohol is common in a large proportion of males who die suddenly and suggest that in addition to the acute consumption also the chronic use of alcohol is an important risk factor in many deaths among middle-aged Finns.
We developed a suitable method for analysing dinucleotide repeats found in the upstream of human alpha-estrogen receptor (ER) gene by applying capillary electrophoresis and automatic analysis. This method omits the gel-casting step as well as difficult handling of long polyacrylamide sequencing gels. Use of radioactive materials is also avoided. Using this method, the frequency distribution of ER alleles, determined in 180 Finnish individuals showed two peaks at 12 and 14 repeats (166 and 168 bp) and also at 22 and 24 repeats (184 and 186 bp). The overall distribution of alleles seemed to be similar to that found among Italian and Japanese populations.
The aim of the study was to determine the pulmonary concentrations of mineral fibers in the Finnish male urban population and to evaluate the analysis of pulmonary fiber burden by scanning electron microscopy (SEM) as an indicator of past fiber exposure.
The pulmonary concentration of mineral fibers was determined by SEM and compared with occupational history for a series of 300 autopsies of urban men aged 33 to 69 years.
The concentration of fibers (f) longer than 1 micron ranged from
Variation in the outcome after aneurysmal subarachnoid hemorrhage (SAH) is not fully explained by known prognostic factors. APOE genotype is the most important genetic determinant of susceptibility to Alzheimer's disease, and it is also shown to be associated with the outcome after traumatic brain injury. We studied the association of apolipoprotein E polymorphism with the outcome after aneurysmal SAH.
A total of 160 consecutive patients were admitted after SAH to a neurosurgical unit. The clinical assessment after the SAH was performed with the Hunt and Hess grading scale. The severity of the bleeding as visualized on CT was assessed by Fisher's grading system. Outcome was assessed with the Glasgow Outcome SCALE: APOE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism.
126 patients had aneurysmatic SAH, and detailed information on outcome and APOE genotype was available for 108 patients (86%). Sixteen (40%) of 40 patients with APOE epsilon4 had an unfavorable outcome compared with 13 (19%) of 68 without the APOE epsilon4 allele (OR 2.8, 95% CI 1.18 to 6.77). Association was more significant after adjustment for age, rebleeding, clinical status on admission, and CT scan findings (OR 7.1, 95% CI 1.9 to 26.3; P=0.0035).
Our findings show a significant genetic association of APOE polymorphism with outcome after spontaneous aneurysmal SAH. Genetic factors thus seem to explain a part of individual differences in the recovery of SAH.
Factor XIII is a transglutaminase that crosslinks fibrin in the last steps of the coagulation process. A few polymorphic sites have been identified in this gene, one of them being a point mutation (FXIII Val34Leu), leading to an amino acid change of valine to leucine. Recently, in British patients, FXIII 34Leu allele was suggested to be associated with a decreased incidence of myocardial infarction (MI). PAI-1 4G/4G genotype seemed to lessen the beneficial effect of FXIII 34Leu allele. The aim of our study was to further investigate the possible protective role of the FXIII 34Leu allele against MI and its suggested interaction with the PAI-1 4G/5G polymorphism. We carried out genotype analyses for FXIII Val34Leu using solid-phase minisequencing in two independent Finnish study groups. In our study, the FXIII 34Leu allele was associated with a lower risk of MI (P = 0.009), however, the PAI-1 4G allele showed no interaction with this polymorphism. To establish the population frequency of the FXIII 34Leu allele and to study the possible variations in Finland four DNA pools from different geographical areas of Finland were genotyped. No significant differences in the allele frequencies were observed (21-28%) except in the Eastern Kainuu area (13%), an area with an increased risk of mortality from coronary artery disease (CAD), supporting the results presented above. The association of FXIII 34Leu variant with a lower incidence of myocardial infarction suggests a new role for FXIII in a polygenic thrombotic disease.
In a consecutive medicolegal necropsy series benign hepatic tumours and tumour like conditions occurred in 52% of the 95 men aged 35-69 years. The incidence increased with age, mainly due to small bile duct tumours (n = 26; mean age 56.7 years; p less than 0.01; mean size 1.3 mm). The next most common tumours were cavernous hemangiomas (n = 19; mean age 53.9 years; mean size 5.2 mm) that were not related to age. Focal nodular hyperplasia (n = 3; mean size 8.0 mm) tended to occur in a younger age group (mean age 40.3 years; p less than 0.001). Multiple bile duct tumours were present in 46% and hemangiomas in 50% of the men studied. Liver cell adenoma, nodular regenerative hyperplasia, and peliosis hepatis were incidental findings (one case of each). Nodular regenerative hyperplasia was associated with the consumption of alcohol and a total dose of 21.5 g of testosterone. These results indicate that benign hepatic tumours and tumour like conditions are not rare in men but may remain undetected because of their small size.
Blood alcohol concentration was determined in 1672 sudden and unexpected natural and non-natural out-of-hospital deaths. The material covered all medicolegal autopsies in the province of Uusimaa which has a population of approximately 1.1 million inhabitants. In general, the prevalence of cases with alcohol in the blood at the time of death was high but varied considerably according to sex, age, and the cause and manner of death. The blood alcohol result was positive in 36% of the male and in 15% of the female material. In 59% of the alcohol-positive male and in 54% of the alcohol-positive female cases the actual concentrations were at least 1.5%. Acute use of alcohol was regarded as a significant condition contributing to death in 23% of the whole male and in 8% of the whole female material. These gross results and the details presented indicate that the acute use of excess alcohol is a factor contributing to non-natural but also to sudden and unexpected natural deaths to an extent that is not generally known. The results also emphasize that simple blood alcohol determination should be a routine procedure in the autopsy praxis of all sudden and unexpected natural and non-natural out-of-hospital deaths.
Chronic low-grade inflammation is involved in the pathogenesis of many disease conditions in humans and it is frequently quantified by measuring the blood concentration of C-reactive protein (CRP). Here we show that the CRP concentration in old people (nonagenarians) is, at least partially, genetically determined, and that the high producer genotype is associated with a shorter life expectancy during follow-up. Thus, the data imply that the CRP gene may be a longevity gene in humans.
Delayed increases in liver cirrhosis mortality and frequency of alcoholic liver cirrhosis following an increment and redistribution of alcohol consumption in Finland: evidence from mortality statistics and autopsy survey covering 8533 cases in 1968-1988.
Changes in the legal restrictions for alcohol consumption in 1969 liberated purchasing and marketing of low-alcohol beer. Subsequently, within the space of 5 years, the per capita consumption of absolute alcohol increased from 4.2 to 6.5 liters. To evaluate the possible effects of this change upon liver cirrhosis mortality as well as prevalence of liver cirrhosis in autopsy series, we surveyed mortality statistics and data from 8,533 medicolegal autopsies in 1968 through 1988. Liver cirrhosis mortality statistics revealed a highly significant (p less than 0.001) increase from 6.4 to 13.7 per 100,000 during the period, and similarly, the prevalence of liver cirrhosis in the autopsy series showed a highly significant (p less than 0.001) increase from 3.0% to 6.1%. More specifically, this increase was attributable to a highly significantly (Chi-square 15.4, p less than 0.001) increased proportion of alcoholic liver cirrhosis occurring at a younger age and almost exclusively in males. The stepwise mode of increase as well as the changes in sex and age distribution of cirrhosis since 1969 could be interpreted as an effect of distribution of consumption to a new generation of consumers. The forensic autopsy series seemed to reflect changes in per capita consumption with a shorter time lag than with mortality statistics. Additionally, only 7% of the 448 cirrhotics singled out from this material exhibited liver cirrhosis as a cause of death and were thus also included in the official mortality statistics, suggesting the greater accuracy of our forensic autopsy series.