Association between Type 2 Diabetes Loci and Measures of Fatness

Type 2 diabetes (T2D) is a metabolic disorder characterized by disturbances of carbohydrate, fat and protein metabolism and insulin resistance.

The majority of T2D patients are obese and obesity by itself may be a cause of insulin resistance. Our aim was to evaluate whether the recently identified T2D risk alleles are associated with human measures of fatness as characterized with Dual Energy X-ray Absorptiometry (DEXA).

Nine single nucleotide polymorphisms (SNPs) in the CDKN2AB, CDKAL1, FTO, HHEX, IGF2BP2,KCNJ11, PPARG, SLC30A8 and TCF7L2 genes were genotyped.

Linear regression was used to study association between individual SNPs and the combined allelic risk score with body mass index (BMI), fat mass index (FMI), fat percentage (FAT), waist circumference (WC) and waist to hip ratio (WHR).

Significant association was observed between rs8050136 (FTO) and BMI (p = 0.003), FMI (p = 0.007) and WC (p = 0.03); fat percentage was borderline significant (p = 0.053). No other SNPs alone or combined in a risk score demonstrated significant association to the measures of fatness.

From the recently identified T2D risk variants only the risk variant of theFTO gene (rs8050136) showed statistically significant association with BMI, FMI, and WC.

Progressi negli strumenti di analisi genetica e medicina personalizzata

Un sofisticato algoritmo computazionale, applicato ad un vasto insieme di marcatori genetici, è riuscito a raggiungere una maggiore accuratezza, rispetto ai metodi convenzionali, nell’individuare il rischio di diabete tipo 1. Un team di ricercatori, guidati dal Dr.Hakonarson, direttore del Center for Applied Genomics presso il Children’s Hospital di Philadelphia, afferma che la loro tecnica applicata ad alcune malattie multigeniche, tra cui il diabete, consente di ottenere miglioramenti nella prospettiva di personalizzare la medicina sulla base del profilo genetico di ciascun individuo. Gli studi di associazione sull’intero genoma (GWAS), nei quali vengono impiegati strumenti automatici che esaminano l’intero genoma umano alla ricerca di varianti genetiche, potrebbero permettere ai medici di predire accuratamente il rischio di ogni individuo relativo ad una specifica malattia e, quindi, guidarli nelle strategie di prevenzione e trattamento.

13 Novembre 2009

New Genetic Variation Linked To Diabetes

Researchers say they have identified a genetic variation in people with type 2 diabetes that affects how the body's muscle cells respond to the hormone insulin. Previous studies have identified several genetic variations in people with type 2 diabetes that affect how insulin is produced in the pancreas. Today's study shows for the first time a genetic variation that seems to impair the ability of the body's muscle cells to use insulin to help them make energy.
People with type 2 diabetes can have problems with the body not producing enough insulin and with cells in the muscles, liver and fat becoming resistant to it. Without sufficient insulin, or if cells cannot use insulin properly, cells are unable to take glucose from the blood and turn it into energy. Until now, scientists had not been able to identify the genetic factors contributing to insulin resistance in type 2 diabetes. In the new research published in Nature Genetics, scientists from international institutions including Imperial College London, McGill University, Canada, CNRS, France, and the University of Copenhagen, Denmark, looked for genetic markers in over 14,000 people and identified four variations associated with type 2 diabetes. One of these was located near a gene called IRS1, which makes a protein that tells the cell to start taking in glucose from the blood when it is activated by insulin. The researchers believe that the variant they have identified interrupts this process, impairing the cells' ability to make energy from glucose. The researchers hope that scientists will be able to target this process to produce new treatments for type 2 diabetes. "It is now clear that several drugs should be used together to control this disease. Our new study provides scientists developing treatments with a straightforward target for a new drug to treat type 2 diabetes," said Froguel. The most significant of these variations was located near the insulin receptor substrate 1, or IRS1, gene.

Article: "A multistage genome-wide association study detects a new risk locus near IRS1 for type 2 diabetes, insulin resistance and hyperinsulinemia", Nature Genetics, 6 September 2009.