Monday, 17 September 2012

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.

3 comments:

  1. I fear we will, until the entire science research budget is swallowed up by these hugely expensive fishing expeditions.

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  2. Level with me guys, is Iran a major player in the world of MS research? Reason I ask is because all we hear about in the Western media is just how primitive and draconian the country is, yet during the Paralympics they had greater representation than nearly all Asian countries bar China. They seem to be a progressive nation that cares for its vulnerable and has invested load of money in exploring MS and trying to improve understanding into the disease.

    How valuable is Iran’s contribution in MS research and are there any embargoes when it comes to the European and American scientific community partnering with them?

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  3. The big players in the world of MS is the USA, Europe and there is a healthy output from Japan and an increasing number from China.

    The middle east has not been considered as a site of much MS because it was south and sunny but that appears to be changing. There appears to be an increasing number of people in Iran that are getting MS and this has an apparent (is that OK Matt) female to male ratio of 5-6:1.

    As countries put more money into their education and health systems the greater there research output becomes. Indeed American Universities are creating out posts in some middle Eastern Countries. I know of guys in the United Arab Emirates where they are exanding their teaching and research and importing US and Europeans scientists. In terms of Iran I do not now allot about thier infrastructure but Prof G has good contacts with some Iranian MS neurologists and we had an Iranian Arm of Team G before he moved on and is now working in the US. There are an increasing number of publications comming from Iran and this I think will increase.

    With regard to embargo I was not award that there was any with regard scientistist collaborating and as you see our Iranian friend had barrier to stop him going to US. Likewise I have met Iranian Neurologists at ECTRIMS.
    The main barrier to movement and employment are work permits and this is a barrier to anyone outside the EU including Iran and the US.

    Because of the apparent increase in MS, then Iranian MSers maybe golddust in helping us explain and find out what causes MS.

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