Multiple Sclerosis Risk Passed Equally By Parents

Recently a phenomenon known as the Carter effect has been put in to doubt. At least for the horrible disease Multiple Sclerosis (MS).

A study published in the journal Neurology last week indicated that the transmission of MS risk is not skewed based on sex.

"Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. The precise nature of these factors and mode of inheritance remains unknown. A female predominance is universally found. Recently, offspring of affected fathers were reported to be more likely to have MS than those of affected mothers. This was attributed to the Carter effect, which is seen in polygenic disorders. The Carter effect predicts that affected parents of the sex lesser affected by a disease/trait are more genetically loaded for risk alleles and thus transmit these more often to their offspring."

The study found that both men AND women afflicted with MS transmitted the disease about 10% of the time to their offspring.

The Sherpa Says: This is a study which calls into question old notions of thinking regarding genetic predisposition. Unless this is a sex linked disease, we should not see skewing. This old thinking was much along the lines of "Only women pass on breast cancer". I am glad to see it go. However the critics of this study will note that 3 times as many afflicted mothers were studied. Also no genome wide association studies have identified any genes in this likely multifactorial disease. Patience......they will come.

Why Watson Didn't Want His ApoE4 Results.

Alzheimer's disease (AD) afflicts about 10% of persons over 65 and almost half of those over 85.

When Jim Watson had his genome sequenced he asked not to have his ApoE4 status revealed. Why??

Dr Watson did not want to know his genotype status because although twin studies suggest that there are several susceptibility genes which, along with the APOE 4 allele, contribute to up to 80% of LOAD (Late Onset Alzheimer's Disease) cases, the story is nowhere near being finished. Not everyone with APOE4 gets Alzheimer's. In fact, the majority do not......

But the picture for those predisposed is getting clearer.

This last week a study was released by the team at TGen (Translational Genomics) in the journal Neuron. According to the study:

"...suggests that the gene - called GAB2 - modifies an individual's risk when associated with other genes, including APOE4. The study results appear in the June 7 issue of the prestigious peer-reviewed journal, Neuron."

"The team screened the DNA from 1,400 individuals who had been clinically assessed with Alzheimer's prior death, and simultaneously examined more than 500,000 SNPs or genetic variations to characterize and confirm additional LOAD susceptibility genes. The search revealed GAB2."

The polymoprhism is known as SNP rs2373115 . It interacts with APO epsilon 4 to prevent neurofibrillary tangles. This protein is over expressed normally in APOE4 afflicted brain cells.

So what does this mean? GAB2 normally acts like your mother. Remember when you made a mess of your room? If you were lucky, your mother cleaned up the mess. You kept making more of a mess and she kept cleaning up. If your mother didn't clean up, then your room was a constant mess. Even worse, you couldn't find anything in your room that you needed. Much like the way an Alzheimers patient can't find their memories.

In the end a Non-cleaning mother and a really messy kid led to a very dirty room. Just like the combination of GAB2's SNP and APOE4 lead to an odds risk of 4.06 a 400% increased risk.

The Sherpa Says: I agree with Jim. ApoE4 testing can often be uninformative with only 25% of those with the gene polymorphisms going on to get Alzheimers. I think family history will have to lead the way. At least until we have a GAB2/ApoE-4/new gene panel that puts together the picture much more clearly.

Family History and Stroke Risk

This week at the American Academy of Neurology's annual meeting results from a study were announced. Persons who had a brother or sister who suffered a stroke were almost 2 times as likely to have a stroke. All strokes in the study were due to an occlusion of a blood vessel which either resolved in less than 24 hours (TIA) or not. Of note the risk to Mexican Americans was even higher. Not surprising to me especially because they have a higher rate of metabolic syndrome in their population. Interestingly this risk was almost 3 fold in Mexican American men! My questions are many fold and will be found out over time. What role do hormones play? What about epigenetic changes in sperm? The list goes on forever.

So once again family history rules the day. I hate to tell all of these testing companies, but family history is the cheapest and best genetic test you have. Now if we can only convince physicians that family history is never noncontributory unless you believe in spontaneous generation!

True there are those like myself with only half a tree and that is where targeted testing guided by a physician will play a role.