Please help me out. I'm hoping I am on the right track. I googled apoe
promoter and found 2 studies, one from 2009 and one from 2011. Are these SNPs that would affect the serum APOE
? I'm a newbie with no biology background so I won't be surprised if I'm way, way off track so please tell me if I am and my feeling will not be hurt. I'm just taking a stab at it.
Based on the 2009 study I'm very concerned about my rs449647 A/A. But then in the 2011 study for which I only have the abstract they focus on the rs405509 G/G, I believe. Does that mean I'm in the clear with my rs449647 A/A?
I need a better brain than mine to figure this out!Can Stavia or someone please provide access to the full text of the 2011 study?2011 Study
-491 rs449647 A/A bad per 2009 study. I am A/A. In the conclusion of this study it does not
say that is bad.
-219 rs405509 G/G bad. I am A/G, which is good.
This study seems to focus on rs405509 G/G as being bad. I can only access the abstract so I'm left wondering what conclusion they reached about rs449647.http://www.ncbi.nlm.nih.gov/pubmed/21263195
J Alzheimers Dis. 2011;24(2):235-45. doi: 10.3233/JAD-2011-101764.
haplotype associated with decreased ε4 expression increases the risk of late onset Alzheimer's disease.
Lescai F1, Chiamenti AM, Codemo A, Pirazzini C, D'Agostino G, Ruaro C, Ghidoni R, Benussi L, Galimberti D, Esposito F, Marchegiani F,Cardelli M, Olivieri F, Nacmias B, Sorbi S, Tagliavini F, Albani D, Martinelli Boneschi F, Binetti G, Santoro A, Forloni G, Scarpini E, Crepaldi G,Gabelli C, Franceschi C.
This paper addresses a tenet of the literature on APOE
, i.e., the relationship between the effects of the ε4, one of the established genetic risk factor for Alzheimer's disease (AD), and its expression levels
as determined by APOE
promoter polymorphisms. Five polymorphisms (-491 rs449647, -427 rs769446, -219 rs405509, and ε rs429358-rs7412) were studied in 1308 AD patients and 1082 control individuals from the Central-Northern Italy. Major findings of the present study are the following: 1) the variants -219T and ε4 increase the risk for late onset AD (LOAD) when they are both present in cis on the same chromosome (in phase); 2) the correlation between the haplotype (-219T/ε4) and AD risk persists when the data are stratified by age; 3) this haplotype likely anticipates the age of onset of the disease. These data, while confirming the association between -219T and AD, highlight the importance of the phase of the alleles for the observed effects on AD risk, suggesting that this information has to be taken into account when assessing the AD genetic risk. Moreover, the data help to clarify the apparent discrepancy that emerges from the genetic analysis where an SNP characterizing the haplotype responsible for an increased risk for LOAD is coherently associated with a reduced expression of ApoE levels
. Our data are compatible with the hypothesis of a complex role of ApoE
in the AD pathogenesis, with positive and negative effects occurring concomitantly according to its expression levels
and its protein-protein interactions largely unclassified.2009 Study
rs449647 A/A bad. I am A/A, which is bad.
-219 rs405509 G/G bad. I am A/G, which is good.http://www.ncbi.nlm.nih.gov/pubmed/19172988?dopt=Abstract
Eur J Hum Genet. 2009 Jul;17(7):938-45. doi: 10.1038/ejhg.2008.263. Epub 2009 Jan 28.
The complex interaction between APOE
promoter and AD: an Italian case-control study.
Bizzarro A1, Seripa D, Acciarri A, Matera MG, Pilotto A, Tiziano FD, Brahe C, Masullo C.
The single nucleotide polymorphisms (SNPs) rs449647, rs769446 and rs405509 in the promoter region of the APOE
gene have been variously suggested to be epsilon 4-independent risk factors for Alzheimer's disease (AD). A previous Italian study found that the rs449647 was significantly associated with late-onset AD. The aim of this study was to verify whether these APOE
promoter SNPs are genetic risk factors for AD and to investigate their interaction with the common APOE
polymorphism. A total of 169 clinically diagnosed AD patients and 99 cognitively intact age-matched controls were included in the study. Significant associations with AD independent from sex, age and APOE
/epsilon 4 status were found for rs449647 A/A and rs405509 G/G genotypes (positive), and rs449647 A/T and rs405509 T/T genotypes (negative). Haplotype frequency estimation at the APOE
locus showed significant associations for the ATG4, ATT4 and ACG3 (positive) and ATT2, ATT3 and TCG3 (negative) haplotypes. Therefore this study confirms the role of the rs449647 A/A genotype as risk factor for AD in Italy and suggests that promoter genotypes and APOE
haplotypes might have a complex function in AD-associated genetic risk factors.