Wednesday, May 20, 2009

Chronic diseases due to infection?

A new paper in the journal PLOS Pathogens, described here, reports that hypertension, or high blood pressure, may be due to infection with cytomegalovirus (CMV) in humans. At least it is in mice, particularly when combined with a high-cholesterol diet. Other viral infections have been associated with hypertension, but the focus in recent years has been on finding genes for high blood pressure.

Most people are infected with CMV--60 to 99%, according to the PLOS paper--and not everyone with CMV has hypertension, but if this new study is correct, it seems to be a significant risk factor. But, as we've discussed repeatedly here, recent attention has been on identifying genetic causation for common diseases, of which hypertension is one. Indeed, schools of public health had all but eliminated infectious disease programs in the '70s and '80s, because we'd conquered infectious diseases (it was rather confidently thought!) and the challenge was now to conquer chronic disease, which first seemed to be an environmental/lifestyle challenge. After that didn't work very well, attention turned to genes (real science--molecules!) and it seemed hopeful that we were going to explain the common complex diseases in genetic terms.

Why the infatuation with genes? Genes follow rules of inheritance, and human genetics was successfully finding genes for rare usually pediatric diseases like PKU or Tay Sachs, and most traits including disease concentrate at least somewhat in families, so it seemed that the same approach should be applicable to chronic disease.

It was clear (though less of interest to geneticists) that even with aggregation in families, environmental factors such as modern inactive over-fed lifestyles etc. could explain a lot. But with some exceptions, the extension of epidemiology to genetics was from concern with environmental exposures, not infection--the 'old' kind of cause that had been beaten by hygiene and vaccinations. But, it may be that a lot of chronic disease is infectious after all--a real lesson in humility if it turns out to be true!

So it turns out that infectious disease biology is a mix of real and important genetics (host, virus, molecular therapy and prevention), as well as the complexities of environmental exposures, plus complexity generally, etc. If genetics resources are concentrated on these kinds of molecular interactions, rather than trying to explain disease risk by host variation (which GWAS and other studies of these diseases clearly show will not be the major cause), then we have some interesting scientific days ahead. This could be--should be--an area where genetic approaches are entirely appropriate rather than forced. The relationships between host and parasite represent battles and evolution at the molecular level--mano a mano among molecules, so it is appropriate to study it at that level.

Paul Ewald has been saying for some time that infectious causes are more important, even for chronic late-onset diseases, than had been thought. He was largely ignored. Maybe he's right!

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