Human Molecular Genetics, Vol 6, 1401-1408, Copyright © 1997 by Oxford University Press
H Zouali, EH Hani, A Philippi, N Vionnet, JS Beckmann, F Demenais and P Froguel
Several candidate genes for non-insulin-dependent diabetes mellitus (NIDDM)
map on chromosome 20, including the phosphoenolpyruvate carboxykinase gene
(PCK1) and one of the maturity onset diabetes of the young genes (MODY1).
Thus, we have investigated the entire long arm of chromosome 20. Linkage
analyses were conducted in a total sample of 148 NIDDM families (301 NIDDM
sib pairs) and in a subset of 42 early onset NIDDM families, where genetic
components are likely to play a more important role (55 NIDDM sib pairs
diagnosed at or before 45 years of age), using 10 highly polymorphic
markers with an average map density of 7.5 cM. Using affected sib pair
methods (two-point linkage and multipoint linkage analyses), significant
results were obtained with the 20q13 region, in the vicinity of the PCK1
locus, only in the subset of 55 early onset NIDDM sib pairs (multipoint MLS
= 2.74, P = 0.0004; MLS = 2.34, P = 0.0009 when using a conservative
weighting procedure). Moreover, another region spanning the ribophorin II
(RPNII, phospholipase C (PLC1) and adenosine deaminase (ADA) loci suggested
linkage with NIDDM (multipoint MLS of 1.81 in all NIDDM sib pairs, P =
0.003; MLS = 1.31, P = 0.012 when using a conservative weighting
procedure). Whereas our study suggests the location of a susceptibility
locus for early onset NIDDM in the PCK1 gene region, further investigation
in larger data sets is required to confirm these results and assess the
role of other regions on chromosome 20q in human NIDDM.
ARTICLES
A susceptibility locus for early-onset non-insulin dependent (type 2) diabetes mellitus maps to chromosome 20q, proximal to the phosphoenolpyruvate carboxykinase gene
Fondation Jean Dausset--CEPH, Paris, France.
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