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From the Joslin Diabetes Center, Section on Epidemiology and Genetics,
Boston, Mass (J.J.R., D.M., M.B.S.F., Y.Y., J.H.W., A.S.K.); Harvard School of
Public Health, Program for Population Genetics, Boston (J.J.R.); and Harvard
Medical School, Department of Medicine, Boston (D.M., M.B.S.F., Y.Y., J.H.W.,
A.S.K.).
Correspondence to John Rogus, ScD, Program for Population Genetics, Harvard School of Public Health, FXB-101, 665 Huntington Ave, Boston, MA 02115-6096. E-mail jrogus{at}ppg.harvard.edu
Abstract—Diabetic nephropathy is a serious and
frequent complication of insulin-dependent diabetes mellitus (IDDM)
that has a strong genetic component. Several case-control studies have
reported conflicting results with regard to the role of
angiotensinogen gene polymorphisms, specifically the
M235T T allele, in the development of diabetic
nephropathy. The primary limitation of the case-control
approach is that bias may be introduced by unrecognized differences in
the populations selected for cases and control subjects. In contrast,
family-based approaches, such as the transmission/disequilibrium test,
assess whether a particular variant, or allele, is transmitted
preferentially from a parent having a single copy of that allele.
Thus each family provides its own control, thereby eliminating spurious
results caused by mismatched population samples. To take advantage of
this study design for further investigation of M235T, we collected from
the Joslin Diabetes Center in Boston 148 IDDM patients with diabetic
nephropathy, 62 nephropathy-free patients with
long-duration IDDM, and, very importantly, parents of all these
individuals. We found that among males (but not females) the T
allele of the M235T polymorphism was transmitted preferentially
to those with nephropathy compared with IDDM patients
without nephropathy (P=.05). Moreover, the T
allele was transmitted preferentially to patients with the most
severe manifestation of nephropathy, end-stage renal
disease (P=.04). In conclusion, results obtained in our
family-based study support a role of the angiotensinogen
gene M235T polymorphism, and specifically the T allele, in the
development of diabetic nephropathy in IDDM.
© 1998 American Heart Association, Inc.
Scientific Contributions
Diabetic Nephropathy Is Associated With AGT Polymorphism T235
Results of a Family-Based Study
Key Words: angiotensinogen • nephropathy, diabetic • diabetes, insulin-dependent
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