Research: not susceptible with APO E lipoprotein genes

Sadeghi et al. Polymorphism of Apo lipoprotein E gene and the risk of multiple sclerosis. J Res Med Sci. 2011;16(12):1519-24.

BACKGROUND: Apolipoprotein E (ApoE) gene encodes an important protein in reforming injuries of central nervous system (CNS). It is assumed that various ApoE alleles may be functionally different. The purpose of this study was to investigate the distribution of ApoE genotypes in multiple sclerosis (MS) patients in a small cohort of Iranians.

METHODS: In this case-control study, blood samples of patients and healthy volunteers were collected (n = 40) from Neurology Clinic of Alzahra Medical Complex. The ApoE genotypes were determined using DNA extracted from the samples by polymerase chain reaction (PCR) techniques followed by digestion with HhaI restriction enzyme. The results were adjusted for age of MS onset, sex, expanded disability status scale (EDSS), and type of MS (primary or secondary progressive). Results were statistically analyzed using chi-square test.

RESULTS: The ApoE3/E3 genotype was detected in the majority of MS patients and the control group. Frequency distribution of E4 allele did not differ significantly between the two groups. There was no difference between ApoE allele and age of disease onset, sex, expanded disability status, or type of multiple sclerosis.

CONCLUSIONS: We found no significant differences in genotype frequency between patients with multiple sclerosis and the control group. Despite the fact that small sample size was a limitation for our study, it seems that ApoE polymorphism may not be useful as a marker for screening patients with multiple sclerosis.

 Apo E is a gene linked to the development of Altzheimers disease. Does it have a role in MS susceptibility, it appears not but I am not sure it would tell us anything other than that because of the same sample size. I do not normally post on these small genetic studies but because of yesterdays post Lay Genetics Does it Confuse I decide to post.


I have heard a prominent MS genetist say that if genetics studies do not contain well over 1,000 samples they are not worth doing. 

It is surely time that the International community of genetic researchers got together and formed some minimal standards of acceptable studies for publication, as underpowered studies just fills journal space and tells us essentially nothing about MS and in some cases may mislead 

However have they got the right answer?

There are a few more papers saying no association





Its not all negative as in this n=197 study

Shi  et al. APOE ε4 is associated with exacerbation of cognitive decline in patients with multiple sclerosis. Cogn Behav Neurol. 2011;24(3):128 ..........but.................


BACKGROUND: Single nucleotide polymorphisms (SNPs) rs429358 (ε4) and rs7412 (ε2), both invoking changes in the amino-acid sequence of the apolipoprotein E (APOE) gene, have previously been tested for association with multiple sclerosis (MS) risk. However, none of these studies was sufficiently powered to detect modest effect sizes at acceptable type-I error rates. As both SNPs are only imperfectly captured on commonly used microarray genotyping platforms, their evaluation in the context of genome-wide association studies has been hindered until recently.

METHODS: We genotyped 12 740 subjects hitherto not studied for their APOE status, imputed raw genotype data from 8739 subjects from five independent genome-wide association studies datasets using the most recent high-resolution reference panels, and extracted genotype data for 8265 subjects from previous candidate gene assessments.

RESULTS: Despite sufficient power to detect associations at genome-wide significance thresholds across a range of ORs, our analyses did not support a role of rs429358 or rs7412 on MS susceptibility. This included meta-analyses of the combined data across 13 913 MS cases and 15 831 controls (OR=0.95, p=0.259, and OR 1.07, p=0.0569, for rs429358 and rs7412, respectively).

CONCLUSION: Given the large sample size of our analyses, it is unlikely that the two APOE missense SNPs studied here exert any relevant effects on MS susceptibility.

So this study looked at over 25,000 and the answer is still no. There have been large genome scans which have not found suceptibility genes.  

Will we have about 25,000 more papers?, as they go through the genome one by one...... Ugh.

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