Linkage analyses of the MODY3 locus on chromosome 12q with late-onset NIDDM.

Non-insulin-dependent diabetes mellitus (NIDDM) is a clinically and genetically heterogeneous disorder. Maturity-onset diabetes of the young (MODY), an autosomal dominant form of NIDDM, has been used as a model for genetic studies of NIDDM. We recently reported linkage between markers on chromosome 12q and diabetes in 25% of our French MODY families. To evaluate if this gene is also implicated in late-onset NIDDM, we performed linkage studies between two markers of the MODY region and diabetes in 172 families with late-onset NIDDM. Both parametric and nonparametric methods were used in a total of 600 affected sib-pairs. Linkage was rejected in this population by all methods, implying that the MODY gene on chromosome 12q is not a major gene for late-onset NIDDM in this population. However, we cannot exclude a modifying role in a polygenic disorder or an important role in some families.