A groundbreaking study published in Communications Medicine has identified rare genetic variants that contribute to the higher prevalence of Type 2 diabetes in Asian Indian families. This discovery opens new possibilities for personalized treatments for diabetes, a condition influenced by both genetic and environmental factors.
Lead researcher Dharambir Sanghera, Ph.D., a professor of pediatric genetics at the University of Oklahoma College of Medicine, explained that the study focused on multiple generations of Asian Indian families, a group known to be at a significantly higher risk of developing Type 2 diabetes—up to six times more than Europeans. The clustering of families and the practice of marrying within the same caste helped the team identify unique genetic variants in these populations.
“Our research found rare gene changes specific to Asian Indian families, which are not present in unrelated populations worldwide,” Sanghera stated. “This is crucial as it sheds light on the diverse genetic causes of diabetes and could guide the development of new, more effective treatments. Tailored therapies are essential, especially since not all patients respond well to current treatments like metformin.”
Type 2 diabetes is influenced by both genetic and lifestyle factors, with genes contributing about 50% to the onset of the disease. The study identified rare genetic variants in an oligogenic pattern, where a few key genes play a significant role, regardless of lifestyle. This contrasts with polygenic diabetes, where many genes contribute small effects, compounded by environmental factors. Unlike previous studies, which primarily focused on European populations, Sanghera’s team examined Asian Indian families to uncover these unique genetic variations.
In an unexpected twist, the researchers discovered that many of the variants were non-coding. While coding genes act as “recipes” for producing proteins, non-coding genes regulate when and where these proteins are made. This finding challenges earlier assumptions that genetic variants linked to diabetes would be coding genes directly involved in disease susceptibility.
“These non-coding variants, found in a few genes, strongly correlate with diabetes in these families, marking an example of oligogenic diabetes,” said Sanghera. “The discovery is significant as it suggests the genetic pathways influencing diabetes may be more complex than previously thought.”
Additionally, the study identified that some of the genes with rare variations were also linked to maturity-onset diabetes of the young (MODY), a monogenic form of diabetes. MODY occurs regardless of lifestyle, and about 14 genes are known to cause this condition in young adults. However, their connection to Type 2 diabetes has not been well understood until now.
Sanghera emphasized that the findings suggest a need for further research into the role of MODY genes in Type 2 diabetes, particularly in families with a history of late-onset diabetes. She noted that families with many cases of Type 2 diabetes and rare non-coding variants showed fewer common genetic risk factors, a deviation from the typical pattern seen in polygenic diabetes.
“The genetic landscape of diabetes is highly complex, much like the heterogeneity seen in breast cancer, where different subtypes require different treatments,” Sanghera concluded. “As we deepen our understanding of diabetes genetics, we move closer to the goal of precision medicine—treating patients according to the specific genetic causes of their diabetes.”
This study marks a significant step forward in understanding the genetic underpinnings of Type 2 diabetes, especially in populations that have been underrepresented in prior research, and could pave the way for more effective, personalized treatment strategies.
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