Patients with type 2 diabetes were more likely to have genetic variations for a key protein regulating cells' insulin receptors, according to a multinational case-control study.
The variants' presence could serve as an early predictive marker of insulin resistance and type 2 diabetes, particularly in patients with a family history of the disease, the study's authors noted.
The investigators examined variations in the high-mobility group A1 protein, or HMGA1, a key regulator of insulin receptor gene expression. The protein's most frequent functional variant was found in 7.2% of the study's 3,278 Italian patients with type 2 diabetes, compared with 0.4% and 3.3% of two Italian control groups (2,544 and 784 patients) without diabetes, significant differences resulting in adjusted odds ratios of 15.8 and 2.0, respectively.
In addition, the variant was found in 7.7% of 970 U.S. case patients, compared with 4.7% of 958 U.S. control patients (adjusted odds ratio, 1.6), a significant difference, and in 7.6% of 354 French case patients vs. 0% of 50 French controls, also a significant difference, reported Dr. Eusebio Chiefari of the University of Catanzaro (Italy) and colleagues (JAMA 2011;305:903-12).
Three other functional variants also were observed in the Italian population, although those variants were not studied in the U.S. and French populations because of the relatively small sample sizes.
Overall, when all four variants were analyzed, nearly 10% of Italian patients with type 2 diabetes were found to have HMGA1 defects, compared with less than 1% of controls.
The four variants of the HMGA1 gene were also shown to be associated with decreased insulin receptor gene and insulin receptor protein expression.
The authors reported no disclosures. Telethon-Italy, MIUR Italy, and the U.S. National Institutes of Health providing funding for the study.