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11.
12.
Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer's disease 总被引:5,自引:2,他引:5
The allelic frequency of the gene for the K variant of
butyrylcholinesterase (BCHE-K) was 0.17 in 74 subjects with late-onset (age
> 65 years) histopathologically diagnosed Alzheimer's disease (AD),
which was higher than the frequencies in 104 elderly control subjects
(0.09), in 14 early-onset cases of confirmed AD (0.07) and in 29 confirmed
cases of other dementia (0.10). The association of BCHE-K with late-onset
AD was limited to carriers of the epsilon 4 allele of the apolipoprotein E
gene (APOE), among whom the presence of BCHE-K gave an odds ratio of
confirmed late-onset AD of 6.9 (95% C.I. 1.65-29) in subjects > 65 years
and of 12.8 (1.9-86) in subjects > 75 years. In APOE epsilon 4 carriers
over 75 years, only 1/22 controls, compared with 10/24 confirmed late-onset
AD cases, had BCHE-K. We suggest that BCHE-K, or a nearby gene on
chromosome 3, acts in synergy with APOE epsilon 4 as a susceptibility gene
for late-onset AD.
相似文献
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DL?MagerEmail author AD?Haffajee PM?Devlin CM?Norris MR?Posner JM?Goodson 《Journal of translational medicine》2005,3(1):27
Background
The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls. 相似文献15.
Ionizing radiation is a carcinogen that induces oxidative DNA damage. 8-
Hydroxy-2'-deoxyguanosine (8-OHdG) is a relatively abundant, mutagenic
lesion that is widely regarded as a reliable index of oxidative DNA damage.
The purpose of this study was to examine the effects of X- radiation on
levels of 8-OHdG in the context of an experimental model for breast cancer
in which chronic radiation exposure has been shown to be carcinogenic in
Sprague-Dawley rats. A secondary objective of this study was to determine
if the use of phenol during DNA isolation affected the concentration of
8-OHdG subsequently measured. Our results indicate that a profoundly
carcinogenic dose of radiation induced a small but significant increase in
8-OHdG concentration in mammary gland DNA, and that the use of a
phenol-based versus a salt-based method of DNA isolation had no significant
impact on the levels of 8-OHdG detected in either control or irradiated
tissue.
相似文献
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19.
Beta 2-adrenergic receptor polymorphisms and haplotypes are associated with airways hyperresponsiveness among nonsmoking men 总被引:6,自引:0,他引:6
STUDY OBJECTIVE: To investigate the relationship of common single nucleotide polymorphisms (SNPs) of the beta(2)-adrenergic receptor (AR) gene at codons 16 and 27, and the intermediate phenotype of airways hyperresponsiveness. DESIGN: A case-control study in 543 white men (152 case patients and 391 control subjects), who were nested in an ongoing longitudinal cohort. SETTING: Subjects were selected from the Normative Aging Study, an ongoing longitudinal cohort of healthy aging. PARTICIPANTS: Case patients were defined as those having a positive response to methacholine challenge testing. Control subjects were selected among those who did not have a diagnosis of asthma and who had no response to methacholine. RESULTS: There was a trend for an association of the Arg16 SNP genotype with airways hyperresponsiveness (odds ratio, 1.25; 95% confidence interval, 0.96 to 1.64 [in an additive model]). In stratified analyses, the effect of the Arg16 variant was seen mainly among nonsmokers. Smokers had increased risks for airway hyperresponsiveness regardless of genotype at either SNP. Using a program to estimate haplotype frequencies, three common haplotypes were identified. Adjusting for age, baseline FEV(1), serum IgE level, and smoking status, the Gly16/Gln27 haplotype was negatively associated with airways hyperresponsiveness in the full complement of case patients and control subjects (score statistic, - 2.43; p = 0.02). The effect of the beta(2)-AR haplotypes was much stronger among lifelong nonsmokers, among whom the Gly16/Gln27 haplotype remained negatively associated with airways hyperresponsiveness (score statistic, - 3.114; p = 0.002), whereas the Arg16/Gln27 haplotype was positively associated with airways hyperresponsiveness (score statistic, 3.142; p = 0.002). No effects were seen among ever-smokers. CONCLUSIONS: In this cohort of middle-aged to older white men, beta(2)-AR polymorphisms were associated with airways hyperresponsiveness, particularly among lifelong nonsmokers. Our results illustrate an instance in which greater power is obtained by performing haplotype analyses as opposed to single SNP analysis. 相似文献
20.
Yamashita T; Wu N; Kupfer G; Corless C; Joenje H; Grompe M; D'Andrea AD 《Blood》1996,87(10):4424-4432
Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and cancer susceptibility. Mutations within the FA complementation group C (FAC) gene account for approximately 14% of diagnosed FA cases. Two mutations, one in exon 1 (delG322) and one in exon 4 (IVS4 + 4 A to T), account for 90% of known FAC mutations. The delG322 mutation results in a mild FA phenotype, while the IVS4 + 4 A to T mutation results in severe FA phenotype. To determine the molecular basis for this clinical variability, we analyzed patient-derived cell lines for the expression of characteristic mutant FAC polypeptides. All cell lines with the delG322 mutation expressed a 50-kD FAC polypeptides, FRP-50 (FAC-related protein), shown to be an amino terminal truncated isoform of FAC reinitiated at methionine 55. All cell lines with the IVS4 + 4 A to T mutation lacked FRP-50. Overexpression of a cDNA encoding FRP-50 in an FA(C) cell line resulted in partial correction of mitomycin C sensitivity. In conclusion, expression of an amino terminal truncated FAC protein accounts, at least in part, for the clinical heterogeneity among FA(C) patients. 相似文献