Review for 10.1186/1471-230X-11-124 (2011)

Reviewer's report
Title:Lactase non-persistent genotype influences milk consumption and
gastrointestinal symptoms in Northern Russians
Version: 2Date:26 June 2011
Reviewer: Mauro Congia
Reviewer's report:
The questions posed by the authors are well defined; i.e. they wanted to
demonstrate that the -13910C/C variant induces in carriers a reduction of milk
consumption due to the trigger of gastrointestinal (GI) symptoms following milk
ingestion. To demonstrate their hypothesis a questionnaire covering personal
data, self-reported GI symptoms and milk consumption habits was administered
to a group of 518 students in whom the -13910C/T polymorphism was
genotyped.
Major Compulsory Revisions
The methods are appropriate and well described but I think the data also in this
revised version sound weak. For instance, the authors claim that the questions of
milk consumption and GI symptoms following milk intake were kept separated
also in drawing the statistical comparisons. In contrast to this, they state in the
discussion “we may conclude that subjects with -13910C/C have more symptoms
from milk and they avoid using milk. Both of our hypotheses were thus verified.”
implying a strict relationship between the two questions and LNP genotype.
There would be nothing to argue if the 24 subjects reporting GI symptoms were
found among the 122 individuals with “less than daily or none” category of milk
consumption, but unfortunately the study design does not allow to answer this
simple question. In other words and paradoxically, all the 24 subjects referring
symptoms after milk ingestion could belong to the category with daily ingestion of
milk and not to the category with less than daily or none milk consumption.
In addition we don’t know which are the GI symptoms that these 24 LNP
individuals are referring following milk ingestion. Were those typical of lactose
intolerance (flatulence, diarrhea, gurgling, abdominal distension and abdominal
cramping) or reported in table 1 where the main GI symptom was stomachache
that is not usually reported in lactose intolerance? Therefore I insist that the
authors should adopt in the discussion a generally more prudent attitude.
Another limitation of the paper that the authors should underscore is the fact that
both LP and LNP subjects have a low milk intake. Therefore, also the statement
“the results demonstrate that Northern Russians with -13910C/C avoid using
even small amounts of milk” is again incoherent because also the majority of
people with LP (58%) have “less than daily or none milk consumption.” that
obviously cannot be explained by the -13910C/T polymorphism.
In addition, for this peculiar finding they provide some not completely satisfactory
explanations. The “cultural preference hypothesis” is not entirely challenged from
the statement “The region where this study was made has been considered as
one of the country’s milk and meat production areas”. Indeed, the actual region of
origin of the 518 students is not specified and as far as I may understand,
students might also come from Russian areas in which there is a culture not
based on high milk consumption. In addition, it has been clearly established that
gene culture coevolution between cow milk intake and the LP genotype is based
on millenary pastoralism in that region (Gene-culture coevolution between cattle
milk protein genes and human lactase genes; NATURE GENETICS VOLUME 35
| NUMBER 4 | DECEMBER 2003). The authors in their cultural hypothesis do not
specify if the area in which the study took place is based on ancient or recent
cattle farmer settlement.
Therefore, the discussion and conclusions should be better balanced with what
the data may support.
I appreciate that the authors have changed the title and deleted “dairy products”
from the test, however I think that the writing still needs some revision from a
native speaker.
I think that the very important result of this paper, not sufficiently stressed by the
authors, is that there is a very low consumption of milk among young people in
Russia that is not explained by the -13910C/C variant. Indeed, also people with
the LP phenotype avoid for unknown reasons milk intake. I hope that in a future
work they will try to address this observation which in my opinion is much more
important than attributing a reduced milk intake to doubtful GI symptoms
associated to the -13910C/C variant.
Minor Essential Revisions
The first paragraph of the results section contains an error in the calculation of
the percentages. “The prevalence of the -13910C/C genotype (lactase
non-persistence, LNP) among 518 young students from North-West Russia was
found to be 34.7% (n = 180) while the -13910C/T genotype was found in 45.9%
and -13910T/T in 19.3% of participants.”
Indeed the sum of 34.7+ 45.9+ 19.3 is 99.9% and not 100%; please correct
accordingly.
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests' below.