In Caucasians,
maturity-onset diabetes of the young (
MODY) is mostly caused by mutations in the
hepatocyte nuclear factor (HNF)-1alpha (
MODY3) and
glucokinase (
MODY2) genes. Most Japanese
MODY patients, however, are not linked to known
MODY genes. In this study, we examined the genetic and clinical characteristics of Chinese subjects with
MODY. The study included 146 unrelated families fulfilling the minimum criteria for
MODY: two consecutive generations of type II diabetes with at least one member diagnosed under the age of 25. We screened for mutations in the HNF-4alpha (
MODY1),
MODY2 and
MODY3 genes by direct sequencing. Antibody to
glutamic acid decarboxylase (GAD-Ab) was measured in subjects with
MODY of unknown cause (MODYX).
Insulin resistance index and other clinical data were compared in sex-, age- and duration-matched
MODY3 and MODYX patients. In all, 13 families had
MODY3 mutations and two had
MODY2 mutations. No
MODY1 mutation was found. Four of the 12 different
MODY3 mutations were newly identified novel mutations (Q243E, A311D, P379R and P488fsdelC). In subjects with MODYX, 3% were GAD-Ab positive and 60% were
overweight. Compared to
MODY3 patients, MODYX patients had higher body mass index (P<0.02), higher
insulin resistance index (P=0.001) and
triglyceride level (P<0.02), lower HDL level (P=0.001) and more
hypertension (P<0.05), but no significant difference in the prevalence of
diabetic complications. In conclusion,
MODY3 and
MODY2 account for only 9 and 1%, respectively, of Chinese
MODY. A majority of Chinese
MODY patients are due to defects in unknown genes and appear to be characterized by
insulin resistance.