5-Hydroxytryptamine 6 receptor (5-HT6) receptor and apolipoprotein E (ApoE) polymorphisms in patients with Alzheimer's disease in the Basque Country

Álvarez-Álvarez, Maite; Galdos, Luis; Fernández-Martı́nez, Manuel; Gómez-Busto, Fernando; Garcı́a-Centeno, Victoria; Arias-Arias, Caridad; Sánchez-Salazar, Carmen; Rodríguez-Martínez, Ana B.; Zarranz, J.J.; Pancorbo, Marian M. de

doi:10.1016/s0304-3940(02)01425-8

Cited by 18 publications

(14 citation statements)

References 12 publications

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“…In the majority of the studies carried out on LOAD, the presence of the APOE 4 allele has been associated with a higher risk of suffering from AD; however, the presence of this allele does not necessarily lead to the development of the disease, as there are many patients with LOAD who do not have the APOE 4 allele [9,28] . In our study, we too have observed that there is also a high incidence of the APOE 3 allele in individuals with LOAD ( table 1 ), hence other genic factors associated with LOAD must exist.…”

Section: Discussionmentioning

confidence: 99%

“…APOE was amplifi ed with the primers 112F and 158R, in the PCR conditions described by Wilton and Lim [21] . Digestion of the amplifi ed product was carried out with Hae II and Afl III as described by Álvarez-Álvarez et al [9] .…”

Section: Genetic Studiesmentioning

confidence: 99%

“…This implies the existence of other genetic susceptibility factors associated with LOAD [9] . Among these might be the CYP46A1 (14q32.1) gene, which encodes the cholesterol 24S-hydroxylase enzyme belonging to the P450 cytochrome family, mainly expressed in the brain [10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

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Polymorphism in the Cholesterol 24S-Hydroxylase Gene (CYP46A1) Associated with the APOEυ3 Allele Increases the Risk of Alzheimer’s Disease and of Mild Cognitive Impairment Progressing to Alzheimer’s Disease

Pozo

Álvarez

Martínez

et al. 2006

Dement Geriatr Cogn Disord

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Background: Late-onset Alzheimer’s disease (LOAD) is associated with changes in certain proteins, such as ApoE and Cyp46A1, of the elimination route for cerebral cholesterol. The main lipoprotein involved in its transport is ApoE whose υ4 allele is the least efficient. However, the presence or absence of this allele does not determine the development of LOAD, which implies the existence of other susceptibility factors associated with the disease, such as the CYP46A1 gene that encodes the enzyme cholesterol 24S-hydroxylase. Objective: To find new data to contribute to the evaluation of whether the presence of the T allele in the polymorphic site rs754203 of the CYP46A1 gene leads to a greater risk of developing mild cognitive impairment (MCI) and LOAD. Furthermore, given the link between APOE and CYP46A1, we proceeded to relate both genotypes in each of the patient groups studied. Methods: We studied MCI and LOAD patients and also carried out an analysis of those MCI patients who progressed from a mild cognitive deterioration to a clinically evident Alzheimer’s disease during the study. Results: The frequency of the CYP46A1-T allele in the LOAD patients with APOEυ3 alleles is significantly higher with respect to the control group; the same occurs in the group made up of LOAD patients together with the MCI patients who progressed to LOAD. The risk of developing LOAD when this allelic combination exists is 2.262 times higher (95% CI 1.337–4.202). However, having the CYP46A1-T allele does not increase the risk of suffering from LOAD in carriers of the APOEυ4 allele, probably because the transport of cholesterol is already affected in such patients and possibly masks the effect of the CYP46A1-T allele. Conclusions: The CYP46A1-T allele increases the risk of suffering from LOAD in persons carrying the APOEυ3 allele.

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Section: Discussionmentioning

confidence: 99%

Section: Genetic Studiesmentioning

confidence: 99%

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Polymorphism in the Cholesterol 24S-Hydroxylase Gene (CYP46A1) Associated with the APOEυ3 Allele Increases the Risk of Alzheimer’s Disease and of Mild Cognitive Impairment Progressing to Alzheimer’s Disease

Pozo

Álvarez

Martínez

et al. 2006

Dement Geriatr Cogn Disord

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“…Digestion of the amplified product was carried out with Hae II and Afl III, as described by Álvarez-Álvarez et al [43]. …”

Section: Methodsmentioning

confidence: 99%

Progression from Amnesic Mild Cognitive Impairment to Alzheimer’s Disease: ESR1 and ESR2 Polymorphisms and APOE Gene

Martín

Martínez²,

Alcelay³

et al. 2011

Dement Geriatr Cogn Disord

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Background: Many genes have been studied to determine how they might be involved in Alzheimer’s disease (AD). Estrogens have a protective effect in the central nervous system. The mechanisms of action of estrogens are mediated by two estrogen receptors (ERs), ERα and ERβ. Thus, these genes could also play a role in the progression of amnesic mild cognitive impairment (MCIa) to AD. The aim of this study was to examine the role of ER single nucleotide polymorphisms (SNPs) as a risk factor for MCIa, as well as the interaction with apolipoprotein E (APOE) Ε4 in the progression to AD. Methods: 79 MCIa patients and 138 healthy controls were analyzed. SNPs were genotyped via restriction fragment length polymorphisms and real-time PCR, RT-PCR or RT-PCR (TaqMan) assays. Results: There is a lack of association between MCIa patients who converted to AD and ER SNPs. APOE Ε4 allele is an independent risk factor of MCIa (OR = 1.86; 95% CI = 1.02–3.38, p = 0.042) with a high prevalence in converted subjects. APOE Ε4 is able to predict the progression from MCIa patients to AD (OR = 2.55; 95% CI = 1.20–5.42, p = 0.015). Conclusions: The presence of the APOE Ε4 allele, and not the alleles of ER SNPs, is a risk factor for MCIa. Furthermore, APOE genotype seems to predict the conversion from MCIa to AD.

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“…41 Digestion of the amplified product was carried out with Hae II and Afl III, as described by Álvarez-Álvarez et al 42 Three single nucleotide polymorphisms (SNPs) in the ESR1 gene (rs9340799, rs2234693 and rs2228480) and one SNP in the ESR2 gene (rs4986938) were evaluated. The first two SNPs in ESR1 (rs9340799 and rs2234693) are in intron 1 and are separated by only 46 base pairs.…”

Section: Genetic Analysismentioning

confidence: 99%

Oestrogen receptor polymorphisms are an associated risk factor for mild cognitive impairment and Alzheimer disease in women APOE ɛ4 carriers: a case–control study

Fernández-Martı́nez

Martín

et al. 2013

BMJ Open

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ObjectivesExamine the role of single nucleotide polymorphisms (SNPs) in the oestrogen receptor (ER) genes: rs9340799, rs2234693, rs2228480 (in the ESR1 gene) and rs4986938 (in the ESR2 gene) as a risk factor for amnesic mild cognitive impairment (MCIa) and Alzheimer's disease (AD) and its possible association with the apolipoprotein E (APOE) gene.DesignWe have investigated the independent and combined association of different alleles of the oestrogen receptor genes and APOE*ɛ4 allele with cognitive impairment using a case–control design.SettingParticipants were prospectively recruited from the neurology departments of several Basque Country hospitals.ParticipantsThis study comprised 816 Caucasian participants who were aged 50 years and older: 204 MCIa, 350 sporadic patients with AD and 262 healthy controls.Primary and secondary outcome measuresClinical criteria and neuropsychological tests were used to establish the diagnostic groups (MCIa, AD and healthy controls). A dichotomous variable was used for each allele and genotype and the association with MCIa and AD was established using Logistic Regression Models.ResultsNeither alleles nor genotypes of SNPs rs9340799, rs2234693, rs2228480 and rs4986938 of oestrogen receptor genes (ESR1 and ESR2) are independently associated with the risk of MCIa or AD. However, the genetic profile created with the combination of the less represented alleles of these SNPs (expressed as XPAA) was associated with an increased risk for MCIa (OR=3.30, 95% CI 1.28 to 8.54, p=0.014) and AD (OR=5.16, 95% CI 2.19 to 12.14, p<0.001) in women APOE*ɛ4 allele carriers.ConclusionsThe less represented alleles of SNPs studied are associated with MCIa and AD in APOE*E4 carriers. In particular, the genetic profile created with the less represented alleles of ESR1 and ESR2 SNPs are associated with an increased risk for MCIa and AD in women APOEɛ4 allele carriers.

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5-Hydroxytryptamine 6 receptor (5-HT6) receptor and apolipoprotein E (ApoE) polymorphisms in patients with Alzheimer's disease in the Basque Country

Cited by 18 publications

References 12 publications

Polymorphism in the Cholesterol 24S-Hydroxylase Gene (CYP46A1) Associated with the APOEυ3 Allele Increases the Risk of Alzheimer’s Disease and of Mild Cognitive Impairment Progressing to Alzheimer’s Disease

Polymorphism in the Cholesterol 24S-Hydroxylase Gene (CYP46A1) Associated with the APOEυ3 Allele Increases the Risk of Alzheimer’s Disease and of Mild Cognitive Impairment Progressing to Alzheimer’s Disease

Progression from Amnesic Mild Cognitive Impairment to Alzheimer’s Disease: <i>ESR1</i> and <i>ESR2</i> Polymorphisms and <i>APOE</i> Gene

Oestrogen receptor polymorphisms are an associated risk factor for mild cognitive impairment and Alzheimer disease in women APOE ɛ4 carriers: a case–control study

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