Diabetes mellitus is a group of metabolic disorders characterized by
hyperglycemia resulting from defects in insulin secretion,
insulin action or both. Genetic factors contribute to the development of diabetes. Some forms such as the condition called
maturity-onset diabetes of the young(
MODY) result from mutations in a single gene. Other forms such as type 1 or
type 2 diabetes are multifactorial in origin with different combinations of genes together with non-genetic factors contributing to the development of
hyperglycemia.
MODY has been a good model for studying the genetics and pathophysiology of diabetes. This form of diabetes can result from mutations in at least seven different genes: hepatocyte nuclear factor(HNF)-4 alpha/
MODY1,
glucokinase/
MODY2, HNF-1 alpha/
MODY3,
insulin promoter factor(IPF-1)/
MODY4, HNF-1 beta/MODY5, NeuroD1/
MODY6 and Islet(Isl)-1/MODY7. Mutations in HNF-1 alpha/
MODY3 are the most common cause of
MODY in Japanese identified to date accounting for about 15% of cases of
MODY. Mutations in the HNF-4 alpha/
MODY1,
glucokinase/
MODY2, HNF-1 beta/MODY5 and Isl-1/MODY7 genes have also been found in Japanese; however, they are rare causes of
MODY. Clinical studies indicate that patients with
MODY are generally not obese and that all forms of
MODY are characterized by pancreatic beta-cell dysfunction. Patients who have mutations in the HNF-1 beta/MODY5 gene have non-diabetic kidney dysfunction including renal
cysts. Female carriers may also exhibit abnormalities in the upper vagina and uterus. Genetic approach for
type 2 diabetes had done by using non-parameteric linkage analysis such as sibpair analysis which worked well and
NIDDM1 and
NIDDM2 have been identified to date. The responsible gene for
NIDDM1 was recently identified to be
Calpain 10, and SNP43 in this gene could explain all of the evidence for linkage in Mexican American
type 2 diabetes.