Thursday, December 11, 2008

Tradeoff between pathogen resistance and auto-immune response?

I first read about this in one of the earlier papers on European genetic structure where they mention: "a north/south gradient in the incidence of autoimmune diseases has been noted for several continents," and give a reference to this paper which, if I remember correctly, shows differences in incidence of various diseases across Europe and discusses the potential tradeoff between pathogen resistance and auto-immune disorders.

Dan at Genetic Future points out a recent study where they find that the same genetic factors contribute to both celiac disease and type I diabetes (both auto-immune disorders). The study also finds that those with the delta-32 variant of CCR5 (protective of HIV infection) have a lower risk of type I diabetes and celiac disease.
These findings beg the questions: Given the distribution of these diseases across Europe, shouldn't they have controlled for ancestry stratification?, and more generally: Is there a unifying phenotype that can be measured which maps to the underlying factor contributing to all these auto-immune diseases? Why is this phenotype seemingly more prevalent among Northern Europeans? Is there some kind of tradeoff between between pathogen resistance and auto-immune "disorders"?
I must say I'm still unclear about the evidence, if any, for this tradeoff.


Maju said...

Why is this phenotype seemingly more prevalent among Northern Europeans?

I'd think that founder effects. Probably most of the ancestry of those populations comes from a small, not really diverse, genetic pool at the time of colonization of Central and Northern Europe. Even later on, due to climatic restrictions, the population of the far north has never been large (though it must have experienced at least three sustainable expansions: early colonization, Neolithic and High Middle Ages).

Yann Klimentidis said...

come on Maju, humor me, you know I'm an adaptationist! ;)
I can see founder effects for simple Mendelian disorders, but harder to believe for a whole class of auto-immune disorders, don't you think?

EllenQ said...

Yes, they should have absolutely controlled for ancestry stratification. However, this also goes along with some interesting evidence that skin pigmentation and vitamin D levels may be related to immune system function.

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