[ Nutrition ]

Major susceptibility locus for nephropathy in type 1 diabetes on chromosome 3q: results of novel


Nephrogenic diabetes insipidus is a rare hereditary disorder, most commonly transmitted in an X chromosome-linked recessive manner and characterized by the lack of renal response to the action of antidiuretic hormone [Arg8]vasopressin. The role of diabetes mellitus in the etiology of chromosomal anomalies has been infrequently studied. In the present study, we aimed to investigate the frequency of sister chromatid exchange (SCE), chromosomal aberrations (CA) and micronuclei (MN) in type-1 diabetes mellitus patients compared with healthy controls. This study explored the possibility that 6q24 abnormalities might cause early-onset, non-autoimmune diabetes without transient neonatal diabetes. With the positional approach, linkage analysis is used to determine location of disease-linked regions. Proteinuria was detected in 19, 7, 5, and 0% (P = 0.07) of subjects, respectively. These linkage analyses suggest that a genetic element on chromosome 7 and possibly one on chromosome 20 influence susceptibility to diabetic nephropathy but not retinopathy.

Continued investigation of this region for a novel type 1 diabetes susceptibility gene appears justified. To investigate whether AT1 could account for the observed linkage, we sequenced all exons, splicing junctions, and the promoter region and examined the identified polymorphisms/mutations for association with DN using the transmission disequilibrium test. While affected infants recover by three months of age, around 50% will develop type 2 diabetes later in life. Therefore, it is reasonable to consider that CDKN2A/B (rs10757274) not only increases the risk of MI, but also enhances the effects of T2DM on the risk of MI in this study.

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