Absence of association between an intercellular adhesion molecule 1 gene E469K polymorphism and Alzheimer's disease in Finnish patients

Increased expression of intercellular adhesion molecule 1 (ICAM1), a protein known to contribute to inflammatory responses, has been detected in the brain tissue of patients with Alzheimer's disease (AD) and animals modelled to mimic AD or Parkinson's disease (PD). ICAM1 may, thus, be implicated in the pathogenesis of these disorders. Our purpose was to investigate whether genetic variants of the ICAM1 gene have a role in causing susceptibility to AD and/or PD. We genotyped the E469K polymorphism of ICAM1 in 196 AD, 52 PD and 202 control patients of Finnish origin. The distributions of the genotype and allele frequencies of the polymorphism did not differ significantly between the AD, PD or the control patients. We therefore conclude that the E469K polymorphism of ICAM1 is not a risk factor for AD or PD.     

Interleukin 1 alpha gene polymorphism as a susceptibility factor in Alzheimer's disease and its influence on the extent of histopathological hallmark lesions of Alzheimer's disease

We investigated the association of the interleukin 1alpha (IL1A) (-889) C/T polymorphism with Alzheimer's disease (AD) and with the extent of AD histopathological lesions, the senile/neuritic plaques (SPs/NPs) and neurofibrillary tangles. We evaluated 98 neuropathologically confirmed AD patients and 240 controls as well as 146 clinically diagnosed AD patients and 278 controls but found no association of the IL1A C/T polymorphism with AD even after adjustment for the apolipoprotein E (APOE) genotype, gender or age. The extents of AD histopathological lesions were not influenced by the IL1A genotype except after exclusion of the APOE epsilon4 allele, when a trend towards more SPs/NPs was observed in AD patients with the IL1A C/C compared to patients with the T/T genotype. These results do not confirm previous studies which have indicated that the IL1A C/T polymorphism is a susceptibility factor for AD. However, the IL1A C/C genotype might be associated with the progression of SPs/NPs in AD patients, but the effect is weak and obscured by the APOE epsilon4 allele.     

Midlife income,occupation, APOE status,and dementia: a population-based study

OBJECTIVE: To examine the relationship between socioeconomic factors and APOE carrier status on the development of dementia. METHODS: Subjects were derived from random, population-based samples previously studied in surveys carried out in 1972, 1977, 1982, and 1987. After an average follow-up of 21 years, 1449 (73%) subjects aged 65 to 79 years were re-examined in 1998. The diagnosis of dementia among the nonparticipants was derived from patient records of the local hospitals and primary health care clinics. RESULTS: Low income level at old age was related to dementia, but low income level at midlife was not a risk factor for dementia. Dementia was also associated with decreasing income level, from midlife to old age 21 years later, when dementia was diagnosed. A sedentary occupation (office, service, or intellectual work) was associated with a decreased risk for dementia among participants; however, when the nonparticipants were included in the analysis, the associations were no longer significant. Low educational level and the APOE epsilon4 allele independently increased the risk for dementia. CONCLUSIONS: Reduction in income level during follow-up and low income level at old age might be the consequence of a dementing process rather than being associated with risk evolution of dementia.     

MPO and APOEepsilon4 polymorphisms interact to increase risk for AD in Finnish males

BACKGROUND: Myeloperoxidase (MPO) is present in senile plaques and surrounding reactive microglia, but not in normal brain parenchyma. MPO in plaques is highest in APOE epsilon4 carriers, suggesting a functional interaction. An MPO promoter polymorphism (-463G/A) linked to increased MPO expression has been associated with increased risk of AD. METHODS: To further define the possible interaction of MPO and APOE epsilon4, we examined 127 patients with AD and 174 controls from a genetically homogeneous Finnish population. RESULTS: A significantly higher percentage of male patients with AD carried the MPO A and APOE epsilon4 alleles relative to men carrying neither allele (p < 0.001; OR, 11.4; 95% CI, 3.6 to 6.7). Male APOE epsilon4 carriers lacking the MPO A allele had an OR of 3.0 (p = 0.01; 95% CI, 1.3 to 6.9), indicating that MPO A enhances AD risk by 3.8-fold. Age at onset was lower in men carrying the MPO A and APOE epsilon4 alleles (Kaplan-Meier survival analysis; p = 0.01). Also, the MPO AA genotype was associated with selective mortality in men, but not in women. AA genotypes were absent from 159 male patients with AD and controls, representing the expected 5% to 6% in women and male controls younger than age 20. The -463A creates an estrogen receptor binding site that may contribute to these gender differences. CONCLUSIONS: MPO A and APOE epsilon4 alleles interact to increase the risk of AD in men but not in women in this Finnish cohort.     

Lack of association between C-850T polymorphism of the gene encoding tumor necrosis factor-alpha and polycystic ovary syndrome.

In the present study, we determined whether genetic variability in the gene encoding tumor necrosis factor-alpha (TNF-alpha) contributes to individual differences in susceptibility to the development of polycystic ovary syndrome (PCOS). The study involved 87 Caucasian Finnish women with PCOS and 115 healthy control women who were genotyped for the C-850T polymorphism in the TNF-alpha gene promoter. Analysis by chi(2) was used to assess genotype and allele frequency differences between PCOS women and controls. A similar genotype distribution for the C-850T polymorphism was observed in the two groups, with the frequency of the variant T allele being 8.6% in the PCOS group and 9.6% in the control group (p = 0.862). Accordingly, the profile of genotype frequencies was similar in the groups. The observed profiles of allele and genotype frequencies confirm an equilibrium state between C-850T polymorphism and PCOS and suggest that polymorphism of the TNF-alpha gene is unlikely to contribute to the risk of PCOS.     

Microsatellite marker association at chromosome region 2p13 in Finnish patients with preeclampsia and obstetric cholestasis suggests a common risk locus

The pathophysiology of preeclampsia is incompletely understood, but the familial nature of the disease has long been recognized. Recent genome-scan studies have indicated linkage at the p23 region of chromosome 2. We have previously reported microsatellite marker association at chromosome region 2p13 in patients with obstetric cholestasis. We conducted population-based association screening with microsatellite markers to find potential preeclampsia-associated loci on chromosome region 2p13-p12 and to test whether preeclampsia and obstetric cholestasis share a single risk locus. The study was carried out among 115 unrelated control women, 133 preeclamptic women and 57 cholestatic women. Screening with microsatellite markers at the 2p13-p12 region revealed that the marker D2S286 was significantly associated with obstetric cholestasis in the overall association analysis (P=0.03), while it revealed only borderline association with preeclampsia (P=0.08). However, single allele association analysis indicated that both preeclampsia and obstetric cholestasis showed a statistically significant association with a common allele (P < 0.05), which was overrepresented in both the obstetric cholestasis (0.42) and preeclamptic (0.37) groups when compared with the control group (0.28). In conclusion, These findings suggest a possible genetic link between chromosome region 2p13-p12, preeclampsia and obstetric cholestasis. More specifically, these data suggest that there may be a common risk locus associated with both obstetric complications located in the vicinity of the 2p13-p12 association region.     

Fibrinogen and factor VII promoter polymorphisms in women with preeclampsia

OBJECTIVE: To determine whether genetic variability in the promoter regions of the genes encoding fibrinogen and factor VII contribute to individual differences in susceptibility to the development of preeclampsia. METHODS: The study involved 133 preeclamptic and 115 healthy control pregnant women who were genotyped for the G-455A polymorphism in the beta-fibrinogen gene promoter and for a decamer insertion or deletion polymorphism at position -323 in the factor VII gene promoter. We used chi(2) analysis to assess genotype frequency differences between preeclamptic women and controls. RESULTS: The allelic distribution of the fibrinogen A-455G polymorphism was similar in the two groups, with the frequency of the variant A allele being 18.8% in the preeclampsia group and 20.9% in the control group. We did not find any association between the presence of the factor VII insertion allele and preeclampsia (5.6% versus 6.1%). Accordingly, the genotype distribution of the fibrinogen G-455A and factor VII polymorphisms in the preeclamptic and control groups was similar (P =.852 and P =.308). CONCLUSION: The G-455A polymorphism of the fibrinogen gene promoter and the decamer insertion or deletion polymorphism of the factor VII gene promoter are unlikely to be major genetic predisposing factors for preeclampsia in subjects from eastern Finland.