Schalin-Jantti C, Nikula-Ijas P, Huan X, Lehto M, Knudsen P,
Polymorphism of the glycogen synthase gene in hypertensive and
(Jan) 27:67-71 1996
This paper examines the association of Xba I polymorphism of the
gene and essential hypertension among 304 nondiabetic subjects (246
normotensives and 58 hypertensives). The A2 allele was found to be twice
as frequent in hypertensives as compared to normotensives subjects (28% vs
14%, respectively). The greatest frequency of the A2 allele was observed in
hypertensive subjects with a family history of non-insulin dependent
diabetes mellitus (NIDDM) (48%) followed by normotensive subjects with a
family history of NIDDM (26%). By contrast, hypertensive and normotensive
subjects without a family history of NIDDM had low frequencies of the A2
allele (16 and 6%, respectively). Thus, it appears that the association of
the A2 allele to a family history of NIDDM is as strong as the association
of the A2 allele to hypertension.
Normotensive subjects with the A2 allele exhibited similar glucose
tolerance and rates of insulin-stimulated glucose storage as compared to
subjects with the A1 allele. In contrast, in hypertensive subjects with
the A2 allele glucose tolerance was more impaired than in hypertensive
subjects with the A1 allele. Hypertensive subjects with the A2 allele also
had lower rates of insulin
stimulated glucose storage than hypertensives with the A1 allele.
Comment: This paper reports an impressive association of the A2
the glycogen synthase gene to hypertension, especially for hypertensive
subjects with a family history of NIDDM. The authors suggest that a locus
in the glycogen synthase gene region on chromosome 19 may serve as a
"thrifty gene", increasing susceptibility to insulin resistance when
exposed to other environmental or genetic factors. Some issues come to
1) Hypertensive subjects had markedly lower rates of
insulin-stimulated glucose storage than normotensive subjects, independent
of which glycogen synthase allele was present. This suggests that
hypertension per se was associated with impaired insulin-stimulated glucose
storage, and that impaired insulin-stimulated glucose storage was not
dependent on the presence of the A2 allele The authors do not emphasize
(or even run statistics on this finding).
2) There were important
differences in the normotensive and hypertensive subjects studied other
than blood pressure which could have accounted for the differences between
the two populations. The hypertensive subjects were older, had a greater
BMI, higher fasting insulin levels and increased levels of cholesterol, HDL
and triglycerides as compared to normotensive subjects.
3) The fact that
hypertensives with the A2 allele had diminished insulin-stimulated glucose
storage, compared to those with the A1 allele (while there was no
difference in normotensive subjects) suggests that hypertension, or one of
the above mentioned differences could modify the action of the A2 allele of
the glycogen synthase gene.
4) Most of the subjects with the A2 allele were
heterogenic. It needs to be determined which allele is actually expressed
and the relative levels of expression in normotensive and hypertensive
subjects. Further, if both alleles are expressed are there differences in
the A1:A2 ratio between normotensive and hypertensive subjects?
of the strong association of the presence of the A2 allele and a family
history of NIDDM, it would also be of interest to examine in more detail,
glucose tolerance and the rates of insulin-stimulated glucose storage in
hypertensive subjects with and without a family history of NIDDM.
interesting study nevertheless shows that in some hypertensive subjects,
there is a greater impairment of insulin-stimulated glucose storage in
subjects with the A2 allele than in those with the A1 allele.
(Michael LaPointe, Ph.D. and Daniel Batlle, M.D., Northwestern University
Medical School, Chicago)