Raygani Asad Vaisi, Zahrai Mahine, Soltanzadeh Akbar, Doosti Mahmood, Javadi Ebrahim, Pourmotabbed Tayebeh
Department of Medical Biochemistry, Tehran University of Medical Sciences, Tehran, Iran.
Neurosci Lett. 2004 Nov 23;371(2-3):142-6. doi: 10.1016/j.neulet.2004.08.057.
Recent studies indicate that there is a synergic association between butyrylcholinesterase-K variant (BChE-K) and apolipoproteinE-epsilon 4 (ApoE-epsilon 4) to promote risk for Alzheimer's disease (AD). Most subsequently replicative studies have been unable to confirm these finding. We attempted to replicate this finding in 105 AD cases and age and sex matched 129 controls from Tehran population, Iran. The BChE genotype of patients were found to be significantly different from controls (chi(2) = 12.2, d.f. = 2, p = 0.002). The frequency of BChE-K allele was also found to differ significantly in cases compared to controls [24% versus 12% (chi(2) = 20.6, d.f. = 2, p < 0.001)] leading to an increased risk of AD in subjects with this allele (OR = 2.5, 95% CI = 1.64-3.8, p = 0.001). This risk was found to increase from (OR = 2.37, 95% CI = 1.3-4.2, p = 0.006) in subjects less than 75 years old to (OR = 3.16, 95% CI = 1.41-7.1, p = 0.001) in subjects 75 years and older. But, the ApoE-epsilon 4 allele association risk was found to decrease from (OR = 9.5, 95% CI = 3.74-24.1, p = 0.001) in subjects <75 years to (OR = 1.36, 95% CI = 0.49-4.1, p = 0.58) in those subjects 75 years and older. Furthermore, we found a very strong synergic association between BChE-K and ApoE-epsilon 4 OR = 19.1 (95% CI = 428-85.45, p < 0.001). In spite of this, synergism decreased from OR = 36.2 (95% CI = 4.4-296, p = 0.001) in subjects <75 year olds to OR = 6.2 (95% CI = 0.9-72.4, p = 0.06) in subjects > or =75 years. We have found that BChE-K and ApoE-epsilon 4 alleles act synergistically to increase the risk of the late-onset AD, particularly in age group <75 years in Tehran, Iran.
最近的研究表明,丁酰胆碱酯酶-K变体(BChE-K)与载脂蛋白E-ε4(ApoE-ε4)之间存在协同关联,会增加患阿尔茨海默病(AD)的风险。大多数后续的重复性研究都未能证实这些发现。我们试图在来自伊朗德黑兰人群的105例AD病例以及年龄和性别匹配的129名对照中重复这一发现。发现患者的BChE基因型与对照有显著差异(卡方=12.2,自由度=2,p = 0.002)。与对照相比,病例组中BChE-K等位基因的频率也有显著差异[24%对12%(卡方=20.6,自由度=2,p < 0.001)],这导致携带该等位基因的受试者患AD的风险增加(比值比=2.5,95%置信区间=1.64 - 3.8,p = 0.001)。发现这种风险在75岁以下的受试者中从(比值比=2.37,95%置信区间=1.3 - 4.2,p = 0.006)增加到75岁及以上受试者中的(比值比=3.16,95%置信区间=1.41 - 7.1,p = 0.001)。但是,发现ApoE-ε4等位基因的关联风险在75岁以下的受试者中从(比值比=9.5,95%置信区间=3.74 - 24.1,p = 0.001)降至75岁及以上受试者中的(比值比=1.36,95%置信区间=0.49 - 4.1,p = 0.58)。此外,我们发现BChE-K与ApoE-ε4之间存在非常强的协同关联,比值比=19.1(95%置信区间=4.28 - 85.45,p < 0.001)。尽管如此,协同作用在75岁以下的受试者中从比值比=36.2(95%置信区间=4.4 - 296,p = 0.001)降至75岁及以上受试者中的比值比=6.2(95%置信区间=0.9 - 72.4,p = 0.06)。我们发现BChE-K和ApoE-ε4等位基因协同作用增加晚发性AD的风险,特别是在伊朗德黑兰75岁以下的年龄组中。