(Press-News.org) For individuals of white European descent, certain variations of the gene HMGA1 are associated with type 2 diabetes mellitus, according to a study in the March 2 issue of JAMA.
Type 2 diabetes mellitus (DM) is a common metabolic disorder that affects nearly 250 million people worldwide, and is associated with major diabetes-related complications, including retinopathy, kidney disease and cardiovascular disease. Insulin resistance in muscle, liver, and fat tissue is a major feature of most patients with type 2 DM. There is considerable evidence that heredity is a major contributor to the insulin resistance of type 2 DM, according to background information in the article. "However, despite extensive investigations, including studies of candidate genes and the recent genome-wide association studies, the common genetic causes of insulin resistance remain elusive," the authors write. The researchers previously found that the protein HMGA1 is a key regulator of insulin receptor (INSR) gene expression.
Antonio Brunetti, M.D., Ph.D., of the University of Catanzaro, Catanzaro, Italy and colleagues conducted a study to examine the association of HMGA1 gene variants with type 2 DM, and included patients with type 2 DM and controls from 3 populations of white European ancestry. Italian patients with type 2 DM (n = 3,278) and 2 groups of controls (n = 3,328) were attending outpatient clinics and other health care sites in Calabria, Italy, during 2003-2009; U.S. patients with type 2 DM (n = 970) were recruited in Northern California clinics between 1994 and 2005 and controls (n = 958) were senior athletes without DM evaluated in 2004 and 2009; and French patients with type 2 DM (n = 354) and healthy controls (n = 50) were enrolled at the University of Reims in 1992. Genomic DNA was either directly sequenced or analyzed for specific HMGA1 mutations.
The researchers found that the most frequent functional HMGA1 variant, IVS5-13insC, was present in 7 percent to 8 percent of patients with type 2 DM in all 3 populations. The prevalence of this variant was higher among patients with type 2 DM (nearly 16 times higher odds of having this variant) than among controls in the Italian population (7.23 percent vs. 0.43 percent in one control group; and 7.23 percent vs. 3.32 percent in the other control group). In the U.S. population, the prevalence of IVS5-13insC variant was 7.7 percent among patients with type 2 DM vs. 4.7 percent among controls; in the French population, the prevalence of this variant was 7.6 percent among patients with type 2 DM and 0 percent among controls. In the Italian population, 3 other functional variants were observed. When all 4 variants were analyzed, HMGA1 defects were present in 9.8 percent of Italian patients with type 2 DM and 0.6 percent of controls.
"We believe our observation that nearly 10 percent of individuals with type 2 DM have deleterious variations in the gene encoding HMGAl has important clinical implications. First, the presence of these variants could serve as an early predictive marker of both insulin resistance and type 2 DM, especially in those individuals who have a family history of type 2 DM and related conditions. Second, the presence of these variants may predict the response to therapy. … Third, individuals who have functional HMGA1 variants and type 2 DM may have a different clinical course than other patients with type 2 DM, including differences in the development of macrovascular and microvascular complications. Fourth, the search for new therapies for type 2 DM could include agents that upregulate the expression of HMGA1," the authors write.
"In conclusion, our results indicate that variants in the HMGA1 gene are associated with type 2 DM in individuals of white, European descent. Further studies of the HMGAl gene and its variants, including studies in other racial types, are needed to understand the role of HMGA1 in insulin resistance and type 2 DM."
(JAMA. 2011;305[9]903-912. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: HMCA1, A Novel Locus for Type 2 Diabetes Mellitus
In an accompanying editorial, Abhimanyu Garg, M.D., of the University of Texas Southwestern Medical Center, Dallas, comments on the findings of this study.
"With the discovery of novel loci for type 2 DM and development of better understanding of the molecular mechanisms by which these variants affect the susceptibility of diabetes combined with the sophisticated metabolic phenotyping related to beta cell dysfunction, insulin resistance, incretin hormones, hepatic glucose, and lipid metabolism, distinct subtypes of type 2 DM will be recognized more clearly. This information may lead to targeted therapies for various subtypes of type 2 DM. … It is anticipated that the discoveries of novel loci such as HMGA1 will soon be translated into therapeutic decision making, and thereby improve the health of patients with type 2 DM."
###
(JAMA. 2011;305[9]938-939. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Please see the article for additional information, including financial disclosures, funding and support, etc.
To contact Antonio Brunetti, M.D., Ph.D., email brunetti@unicz.it. To contact editorial author Abhimanyu Garg, M.D., call Kristen Holland Shear at 214-648-3404 or email Kristen.hollandshear@utsouthwestern.edu.
For More Information: Contact the JAMA/Archives Media Relations Department at 312-464-JAMA or email: mediarelations@jama-archives.org.
Gene variations associated with risk of type 2 diabetes
2011-03-02
ELSE PRESS RELEASES FROM THIS DATE:
Nitric oxide does not appear to improve treatment of sickle cell pain-attacks
2011-03-02
Among patients with sickle cell disease, treatment of a vaso-occlusive crisis (characterized by episodes of severe pain) in the hospital with inhalation of nitric oxide gas for up to 3 days did not result in a shorter time to resolution of the pain, compared to patients who received placebo, according to a study in the March 2 issue of JAMA.
Vaso-occlusive crisis (VOC) is common among patients with sickle cell disease (SCD), with an average length of hospitalization during VOC of 4.5 days for children ages 10 to 14 years. As many as 20 percent of patients hospitalized ...
A small subset of normal white blood cells gives rise to a rare leukemia, study shows
2011-03-02
COLUMBUS, Ohio – New research has identified a small subset of normal white blood cells in the body that gives rise to a rare incurable form of leukemia.
The study, led by investigators at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), shows that large granular lymphocyte leukemia can occur in a small subset of white blood cells called NKT cells. NKT cells share features of immune cells called T lymphocytes and features of immune cells called natural killer (NK) cells. ...
Gene variants in autism linked to brain development
2011-03-02
New research on the genomics of autism confirms that the genetic roots of the disorder are highly complicated, but that common biological themes underlie this complexity. In the current study, researchers have implicated several new candidate genes and genomic variants as contributors to autism, and conclude that many more remain to be discovered. While the gene alterations are individually very rare, they mostly appear to disrupt genes that play important functional roles in brain development and nerve signaling.
While an association between genomic variants in certain ...
Shark tracking reveals impressive feats of navigation
2011-03-02
Some shark species are able to navigate to specific locations up to 50km away, a new study published in the British Ecological Society's Journal of Animal Ecology has found. Re-analysing tracking data from tagged sharks, ecologists found that while some species such as blacktip reef sharks swim in a pattern known as a "random walk", others such as tiger sharks can at times hunt for prey or mates by using "directed walks", accurately navigating long distances across open ocean, often at night.
To maximise lifetime fitness, animals should optimise search patterns for finding ...
New generation of optical integrated devices for future quantum computers
2011-03-02
A research group led by scientists from the University of Bristol has demonstrated the quantum operation of new components that will enable compact circuits for future photonic quantum computers.
Quantum computers, holding the great promise of tremendous computational power for particular tasks, have been the goal of worldwide efforts by scientists for several years. Tremendous advances have been made but there is still a long way to go.
Building a quantum computer will require a large number of interconnected components – gates – which work in a similar way to the ...
Study finds nitric oxide does not help sickle cell pain crisis
2011-03-02
Inhaling nitric oxide gas does not reduce pain crises or shorten hospital stays in people living with sickle cell disease, according to the results of a new study sponsored by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health.
"Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis," will be published in the March 2 issue of the Journal of the American Medical Association.
Sickle cell disease is an inherited disorder affecting between 70,000 and 100,000 Americans. The disease causes red blood cells, which ...
Cannabis use precedes the onset of psychotic symptoms in young people
2011-03-02
Cannabis use during adolescence and young adulthood increases the risk of psychotic symptoms, while continued cannabis use may increase the risk for psychotic disorder in later life, concludes a new study published on bmj.com today.
Cannabis is the most commonly used illicit drug in the world, particularly among adolescents, and is consistently linked with an increased risk for mental illness. However, it is not clear whether the link between cannabis and psychosis is causal, or whether it is because people with psychosis use cannabis to self medicate their symptoms.
So ...
Smoking increases risk of breast cancer in postmenopausal women
2011-03-02
Postmenopausal women who smoke or used to smoke have up to a 16% higher risk of developing breast cancer compared to women who have never smoked, finds research published on bmj.com today.
The study also says that women who have had extensive exposure to passive smoking, either as children or in adulthood, may also have an excess risk of developing breast cancer.
While some previous studies have indicated that smoking increases the risk of breast cancer, the theory that passive smoking is also a risk factor, remains controversial.
The researchers, led by Dr Juhua ...
Has suspending targets changed waiting times?
2011-03-02
Have the suspension of central performance management of the 18 week referral to treatment target, and a relaxation of the four hour Accident and Emergency target, changed waiting times asks John Appleby, Chief Economist at the King's Fund in this week's BMJ?
The English National Health Service was once notorious for its excessive waiting times. In December 1999, nearly 160,000 patients were still waiting over six months for their first outpatient appointment and over 50,000 were still waiting over a year for a bed in hospital.
But since 2000, tough targets imposed ...
Which symptoms of PTSD do the most damage?
2011-03-02
In the case of post-traumatic stress disorder, not all symptoms are created equal.
In an effort to better treat PTSD, a study published March 1 in the journal Psychiatric Services is the first to examine which problems associated with PTSD actually correspond to lower quality of life, as indicated by the patient's willingness to die sooner or to risk life-threatening treatment to relieve their symptoms.
PTSD is more costly than any other anxiety disorder. As many as 300,000 veterans returning from Iraq and Afghanistan currently have PTSD, with costs for their care estimated ...