Microsatellite polymorphism of the α 1 -antichymotrypsin gene locus associated with sporadic Alzheimer's disease

Morgan, Kevin; Morgan, Linda; Carpenter, K.; Lowe, James; Lam, Letty; Cave, Samantha; Xuereb, John H.; Wischik, Claude M.; Harrington, Charles R.; Kalsheker, Noor

doi:10.1007/s004390050304

Cited by 30 publications

(18 citation statements)

References 16 publications

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“…In contrast to that report we found only weak evidence that the AACT A10 allele was a risk factor for AD. We also found that the OR was higher in the AACT A10-group, unlike the results reported by Morgan et al (1997). In addition, we consider the`test for trend' employed in that study to be inappropriate, and we propose that these authors should have instead performed a test for interaction which would have given a non-signi®cant result (w 2 1.48, df 1, p 0.22).…”

Section: Discussioncontrasting

confidence: 71%

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Association of serum AACT levels and AACT signal polymorphism with late-onset Alzheimer's disease in Northern Ireland

McIlroy

Vahidassr

Savage

et al. 2000

Int. J. Geriat. Psychiatry

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α1‐antichymotrypsin (AACT) is a serine protease inhibitor that has been associated with amyloid plaques in the brains of patients with Alzheimer's disease (AD). It has been reported that AACT serum levels are higher in AD patients than in age and sex matched controls. In addition, polymorphisms in the signal peptide and 5′ of the AACT gene have been reported to increase the risk of developing AD. Serum AACT has also been suggested to be associated with cognitive decline in elderly subjects. Our objective was to investigate whether a relationship existed between serum AACT levels, AACT genotypes and risk for AD in a case control association study using 108 clinically well defined late onset AD cases and 108 age and sex matched controls from Northern Ireland. We also wished to determine whether higher serum AACT affected levels of cognition as had been previously reported. Serum AACT levels were found to be significantly raised in cases compared to controls (t=3.8, df=209, p<0.001). However, we detected no relationship between serum AACT levels and cognitive decline. We report allelic association of the AACT signal polymorphism with AD (χ2=3.70, df=1, p=0.04) but we failed to show any correlation between AACT serum levels and genotype. Copyright © 2000 John Wiley & Sons, Ltd.

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Section: Discussioncontrasting

confidence: 71%

“…H to the AACT gene where the A10 allel in combination with APOE had been reported to signi®cantly increase the risk of developing AD (Morgan et al, 1997). In contrast to that report we found only weak evidence that the AACT A10 allele was a risk factor for AD.…”

Section: Discussioncontrasting

confidence: 60%

Association of serum AACT levels and AACT signal polymorphism with late-onset Alzheimer's disease in Northern Ireland

McIlroy

Vahidassr

Savage

et al. 2000

Int. J. Geriat. Psychiatry

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“…17 There are no significant differences in allele or genotype frequencies of the BChE-K variant between AD and control groups ( Table 2) in contrast to previous findings. 13 Allele and genotype frequencies for the PS-1 intronic polymorphism are shown in Table 3.…”

Section: Resultscontrasting

confidence: 60%

Evaluation of polymorphisms in the presenilin-1 gene and the butyrylcholinesterase gene as risk factors in sporadic Alzheimer's disease

et al. 1999

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The ε4 allele of the apolipoprotein E gene (APOE) is a major risk factor for late-onset Alzheimer's disease (LOAD) but is neither necessary nor sufficient to cause the disease. In this study, we investigated polymorphisms in the presenilin-1 (PS-1), and butyrylcholinesterase (BChE) genes, which have been implicated as risk factors for LOAD. Our data-set comprised 177 AD and 118 control patients, all of whom had been histopathologically confirmed following autopsy. We have tested homozygosity for the PS-1 allele 1 and possession of the BChE-K variant in association with APOE ε4 as risk factors in LOAD. Our findings support an association between the PS-1 polymorphism and LOAD, finding homozygosity for allele 1 associated with an approximately two-fold increased risk. Our data also show that in subjects greater than 75 years of age possession of both BChE-K and APOE-ε4 alleles is associated with an increased risk of LOAD, whilst the risk associated with APOE-ε4 allele alone is not significant.

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“…Although this association was con®rmed in a group of Japanese AD patients [Yoshiiwa et al, 1997], several other groups have not found this association in Caucasian AD patients Muller et al, 1996;Nacmias et al, 1996;Talbot et al, 1996;Didierjean et al, 1997;Helisalmi et al, 1997;Morgan et al, 1997;Murphy et al, 1997;Lamb et al, 1998]. Also, Muramatsu et al [1996] found a nonsigni®cant trend for the AA genotype in Japanese AD patients, which was signi®cant only in non-E4 individuals.…”

Section: Discussionmentioning

confidence: 84%

Investigation of association of 13 polymorphisms in eight genes in southeastern African American Alzheimer disease patients as compared to age‐matched controls

et al. 2001

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Alzheimer disease (AD) is an emotionally devastating and exceptionally costly disease. Apolipoprotein E (APOE) is a major risk factor gene for AD regardless of age of onset or family history. However, this association may not be as strong or consistent in ethnic groups such as African Americans, raising the possibility of other modifier gene(s). In a group of African American AD patients, a significantly increased risk of AD was associated with two E4 alleles (OR = 5.6; 95% CI = 1.5-21.0) or one E4 allele (OR = 2.5; 95% CI = 1.3-5.0) when compared to E3/E3 genotype, and there was a significant lowering of age of onset for affecteds with E4/E4 genotype as compared to one E2 allele (P = 0.02) or all others (P = 0.03). We also found a significant increase in age of onset with the -308 #2 (A) allele of TNF when compared to AD cases with no #2 allele. A significant increase in age was also demonstrated with the #2 allele (99 base pairs) of the microsatellite TNFa, located approximately 10.5 kb upstream of TNF. When these two alleles were combined with the TNF -238G (#1) allele to give a haplotype, the significant increase in age was still demonstrated. Polymorphisms in the APOE promoter and six other candidate genes did not appear to demonstrate any significant association with our African American AD patients. Our results confirm the established association of APOE4 to AD observed in several ethnic groups, including African Americans. In addition, TNF appears to have some modifying effect in AD, primarily on age of onset, or it could be in linkage disequilibrium with a modifier locus nearby.

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Microsatellite polymorphism of the α 1 -antichymotrypsin gene locus associated with sporadic Alzheimer's disease

Cited by 30 publications

References 16 publications

Association of serum AACT levels and AACT signal polymorphism with late-onset Alzheimer's disease in Northern Ireland

Association of serum AACT levels and AACT signal polymorphism with late-onset Alzheimer's disease in Northern Ireland

Evaluation of polymorphisms in the presenilin-1 gene and the butyrylcholinesterase gene as risk factors in sporadic Alzheimer's disease

Investigation of association of 13 polymorphisms in eight genes in southeastern African American Alzheimer disease patients as compared to age‐matched controls

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