Objective: To determine whether mutation of the coding or junction region of glucokinase gene (GCK) is also the pathogenic cause of the common form of non-insulin-dependent diabetes mellitus (NIDDM) in Chinese.
Methods: Single strand conformation polymorphism (SSCP) analysis was performed after the 12 exons and junction regions of GCK of each subject studied were separately amplified with polymerase chain reaction (PCR). The molecular scanning was carried out in 30 Chinese subjects with common form NIDDM having the age of onset at or before 45 years, and/or with positive family history of diabetes mellitus (NIDDM-A group). Further screening of the mutation/variation found was conducted in 56 NIDDM subjects (NIDDM-B group) and 134 non-diabetes subjects (ND group) in order to define their frequencies.
Results: No mutation was found by molecular scanning in coding or junction region of GCK in NIDDM-A group. A variant of intron I b was detected in GCK of NIDDM subjects, especially in those with early age of onset and/or with positive family history of diabetes. Significant difference in incidences was found between ND group and NIDDM-A+B group (0% vs 4.7%, Fisher exact P = 0.022).
Conclusions: (1) Mutation of coding and junction regions of GCK is not the main pathogenic factor of common form NIDDM in Chinese subjects. (2) A variant of GCK intron I b may be found in NIDDM in Chinese, especially in those with early age of onset and/or with positive family history of diabetes. Its role in the expression of GCK remain to be elucidated.