Lactase persistence / Cystic fibrosis tradeoff

Is the high rate of Cystic Fibrosis a by-product of lactose tolerance in Northern Europeans? This new paper in the European Journal of Human Genetics (it's open access) proposes this and provides some data to support it.

Cystic fibrosis and lactase persistence: a possible correlation (FREE)

Guido Modiano, Bianca M Ciminelli and Pier F Pignatti

Eur J Hum Genet advance online publication, December 20, 2006

Apparently, it has long been assumed that there was a heterozygote advantage that maintained the lethal recessive CFTR allele. Here, the authors propose that this advantage consisted of "a resistance to lactose-caused diarrhea in populations that adopted such a habit while they were still lactose intolerant."

First they argue that the high CF allele frequency in Europe (.02) compared to Africa (.01) and Far East Asia (.002) is better explained by a '' 'Europe-restricted' heterozygous advantage" than by a 'Europe-restricted' high mutation rate". (Are these really the only two possible hypotheses?).
As for what theis heterozygote advantage might consist of: "the CFTR protein is the Cl- ion channel responsible for the displacement of ... water from the mucosa epithelial cells into the respiratory and intestinal lumen."

Their time course of events:

1. Initially all humans were lactose intolerant and the cumulative CF gene frequency was maintained at a value of about 0.002 by a _{+ CF}4 10^-6 (as in Japan).
2. 5000–10 000 years ago cattle-breeding and dairy milk post-weaning diet started,^{19, 20} resulting in a stringent selective pressure.
3. The onset of an 'emergency' adaptive response consisting of an immediate expansion of the already available CF alleles (the antiquity of the F508del allele has been estimated to be 52,000 years²¹). They would have attained and maintained a frequency unknown, but possibly higher than the present one, resulting from a balance between the advantage of being more resistant to the adverse consequences of being unable to digest lactose (hence to benefit from an important food as the milk) and a heavy segregational load.
4. The onset of the not costly lactase-persistence adaptation, which attained rapidly a very high frequency (up to fixation in some European areas).^{14, 15}
5. A progressive decrease of the CF gene frequency down to the present (still high) values, which can be considered a relic of the past 'emergency' adaptation.

I think that this paper makes a very compelling case, but may overestimate the strength of selection for lactose persisitence in that it would need this type of "initial emergency segregational load adaptation",... unless of course there was some sort of sudden environmental change that required a desperate need for milk as food - which is possible I suppose... I just think that this paper implies that the strength of selection for lactose tolerance was very high, which is interesting in itself. This idea proposed in this paper definitely deserves some further investigation.