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    <recommendedItem id="20100101_19_391"
                     title="Rare Genetic Deletion Linked to Morbid Obesity (CME/CE)"
                     score="0.011"
                     href="http://www.medpagetoday.com/Genetics/GeneralGenetics/tb/18286?impressionId=1265756617900"
                     
      &lt;p&gt;Missing sections of DNA may have a powerful impact on weight for a small segment of the population, researchers said.&lt;/p&gt;
&lt;p&gt;Nearly all teens and adults found to have a particular deletion of roughly 30-genes on chromosome 16p11.2 were obese  --  most morbidly so  --  with a body mass index of at least 40 kg/m&lt;sup&gt;2&lt;/sup&gt;, Philippe Froguel, MD, PhD, of Imperial College London, and colleagues reported in &lt;em&gt;Nature&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;While the variant appeared to explain only a small proportion of morbid obesity  --  0.7% in the study population  --  it was never present in healthy, normal-weight controls.&lt;/p&gt;
&lt;p&gt;&quot;Although the recent rise in obesity in the developed world is down to an unhealthy environment, with an abundance of unhealthy food and many people taking very little exercise, the difference in the way people respond to this environment is often genetic,&quot; Froguel said in a prepared statement.&lt;/p&gt;
&lt;p&gt;But with further findings like these, it may be possible to identify such individuals through genetic testing, he said.&lt;/p&gt;
&lt;p&gt;If so, &quot;We can then offer them appropriate support and medical interventions, such as the option of weight-loss surgery, to improve their long-term health,&quot; Froguel declared.&lt;/p&gt;
&lt;p&gt;Although researchers speculate that one in 20 cases of obesity may have a genetic cause, the genetic component remains largely elusive.&lt;/p&gt;
&lt;p&gt;Even accounting for such a small fraction of cases, the newly discovered 16p11.2 variant would be the second most frequent known genetic cause of obesity, Froguel&apos;s group said.&lt;/p&gt;
&lt;p&gt;Extensive genome-wide association studies have linked numerous single nucleotide polymorphisms (SNPs) to obesity, but added all together they account for only a small fraction of the known heritable component, the researchers said.&lt;/p&gt;
&lt;p&gt;&quot;The &apos;common disease, common variant&apos; hypothesis is increasingly coming under challenge,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;Their team first identified the genetic deletion in teen and adults with learning difficulties or delayed development.&lt;/p&gt;
&lt;p&gt;Because the 31 individuals who had the nearly identical deletions of at least 593 kilobases at chromosome 16p11.2 in one copy of their DNA all had a BMI of over 30 kg/m&lt;sup&gt;2&lt;/sup&gt;, the researchers decided to dig a little deeper.&lt;/p&gt;
&lt;p&gt;&quot;Cohorts with extreme phenotypes that include obesity may be enriched for rare but very potent risk variants,&quot; making them easier to discover, they wrote.&lt;/p&gt;
&lt;p&gt;So they undertook a case-control study among 312 patients at three centers in Britain and France who presented with congenital malformations, developmental delay, or both, in addition to obesity.&lt;/p&gt;
&lt;p&gt;The same deletions were seen in 2.9% of these individuals.&lt;/p&gt;
&lt;p&gt;The function of the missing genes are not well known, but some have previously been associated with delayed development, autism, and schizophrenia.&lt;/p&gt;
&lt;p&gt;Notably, though, the frequency of deletion of these genes in the obese case-control cohort was &quot;appreciably higher&quot; than the less than 1% seen in the autism and other studies that didn&apos;t include obesity as an inclusion criteria, the researchers said.&lt;/p&gt;
&lt;p&gt;A second independent survey of genetic data at eight cytogenetic centers in France, Switzerland, and Estonia turned up a 0.6% rate among 3,947 people with developmental delay, malformations, or both, but who were not selected for obesity (&lt;em&gt;P&lt;/em&gt;=0.00022 versus the cohort selected for obesity).&lt;/p&gt;
&lt;p&gt;Analysis of those with the missing genes revealed an age-dependent link to weight: All four teens and adults were obese. Children were often obese (four of 15) or overweight (two of 15). Children under 2 years all had normal weight.&lt;/p&gt;
&lt;p&gt;So to see whether the deletion was independent of neurodevelopmental problems, Froguel&apos;s group examined genome-wide association study data from general population cohorts totaling 11,856 individuals along with 2,772 from childhood obesity and adult morbid obesity case-control studies, 931 in an extreme early-onset obesity study, and 141 who had bariatric weight-loss surgery.&lt;/p&gt;
&lt;p&gt;All adult carriers of the deletion were obese with the exception of one who was apparently diabetic. Each of the seven children and adolescents who carried the variant had a BMI in the top 0.1% for their age and gender.&lt;/p&gt;
&lt;p&gt;None had any reported developmental or cognitive problems. Four had reported hyperphagia with excessive hunger and food intake.&lt;/p&gt;
&lt;p&gt;Altogether, the 16p11.2 deletions predicted 29.8-fold elevated risk of obesity (&lt;em&gt;P&lt;/em&gt;=0.00000058) and 43.0-fold elevated risk of morbid obesity (&lt;em&gt;P&lt;/em&gt;=0.000000064) compared with lean or normal weight.&lt;/p&gt;
&lt;p&gt;By extrapolation, the researchers extrapolated that about 0.4% of all morbidly obese cases are attributable to an inherited 16p11.2 deletion, with 0.3% arising from a de novo deletion in the same genetic region.&lt;/p&gt;
&lt;p&gt;&quot;Although they may be heterogeneous in nature, these deletions are highly likely to be the causal variants,&quot; they wrote.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by &quot;Le Conseil Regional Nord Pas de Calais/FEDER&quot; along with various governmental and industry supporters for the various component studies.&lt;/p&gt;&lt;p&gt;The researchers reported no financial conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_1394"
                     title="Underactive Thyroid Linked to Liver Cancer Risk"
                     score="-0.006"
                     href="http://www.medpagetoday.com/Endocrinology/Thyroid/tb/14070?impressionId=1265756617900"
                     
      SAN FRANCISCO, May 6 -- Long-term hypothyroidism may nearly triple the risk of developing liver cancer, researchers found.
              &lt;p&gt; 
              &lt;p&gt;The association was independent of established hepatocellular carcinoma risk factors, but significant only among women, according to Manal M. Hassan, M.D., Ph.D., of the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues.
              &lt;p&gt; 
              &lt;p&gt;These case-control study findings shouldn&apos;t be surprising, the researchers wrote in the May issue of &lt;em&gt;Hepatology&lt;/em&gt;.
              &lt;p&gt; 
              &lt;p&gt;Hypothyroidism has been linked to chronic liver diseases and implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH), which is considered a predisposing condition for liver cancer.
              &lt;p&gt; 
              &lt;p&gt;This may result from the essential role of thyroid hormones in lipid mobilization and degradation and fatty acid oxidation, Dr. Hassan&apos;s group said. When they&apos;re out of balance, &quot;all of these conditions may enhance the susceptibility to chronic inflammation, DNA damage, and hepatocellular carcinoma development.&quot;
              &lt;p&gt; 
              &lt;p&gt;In the study, an underactive thyroid increased hepatocellular carcinoma risk independent of hepatitis C virus (HCV) infection (adjusted odds ratio 2.0, 95% CI 1.2 to 3.3) and independent of diabetes (adjusted OR 1.9, 95% CI 1.2 to 3.3).
              &lt;p&gt; 
              &lt;p&gt;Together, though, these factors appeared to have more than an additive effect (adjusted OR 34.3 for hypothyroidism plus HCV and 7.9 for hypothyroidism plus diabetes, respectively).
              &lt;p&gt; 
              &lt;p&gt;&quot;Screening and proper management of thyroid diseases in patients with diabetes or hepatitis C virus infection may help prevent hepatocellular cancer,&quot; they said.
              &lt;p&gt; 
              &lt;p&gt;The ongoing hospital-based case-control study involved 420 hepatocellular carcinoma patients newly diagnosed at M.D. Anderson. 
              &lt;p&gt; 
              &lt;p&gt;The controls included 1,104 healthy, genetically unrelated family members (such as spouses and in-laws) of M.D. Anderson patients with cancers other than liver, gastrointestinal, lung, or head and neck.
              &lt;p&gt; 
              &lt;p&gt;Overall, more of the hepatocellular carcinoma cases than controls reported a history of thyroid disease (15.0% versus 12.1%). 
              &lt;p&gt; 
              &lt;p&gt;Likewise, a history of hypothyroidism -- the most common type of thyroid disease -- was significantly more common among cases than controls (11.7% versus 8.0%, &lt;em&gt;P&lt;/em&gt;=0.03). 
              &lt;p&gt; 
              &lt;p&gt;Long-term hypothyroidism of more than three-years duration conferred a significant, 2.1-fold excess risk of liver cancer, compared with no history of thyroid disorders. 
              &lt;p&gt; 
              &lt;p&gt;The multivariate analysis found the association only among women.
              &lt;p&gt; 
              &lt;p&gt;Women with a prior, long-term history of hypothyroidism for three to 10 years had a 2.6-fold higher risk of hepatocellular carcinoma (95% CI 1.0 to 7.2). For women with a history of hypothyroidism lasting more than 10 years, the risk was 2.9 times as high (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).
              &lt;p&gt; 
              &lt;p&gt;The two- to threefold increased risk of liver cancer remained for hypothyroidism in analyses controlling for obesity at different ages, for all established hepatocellular carcinoma risk factors, and even in analyses restricted to nondrinkers, nonsmokers, and those without hepatitis or diabetes.
              &lt;p&gt; 
              &lt;p&gt;The greater susceptibility of women than men with the same condition may be partially explained by the liver&apos;s role as a major target tissue for the proliferative effect of growth hormones, their receptors, and binding protein, the researchers suggested.
              &lt;p&gt; 
              &lt;p&gt;They noted that further prospective study is needed in different populations to validate the findings and to determine the underlying mechanisms.
              &lt;p&gt; 
              &lt;p&gt;While the self-reported thyroid disease may have been prone to recall bias, the investigators found no discrepancy in the medical records.
              &lt;p&gt; 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt;The study was supported by National Institutes of Health grants and the Texas Tobacco Settlement. The researchers reported no conflicts of interest.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
       
    </recommendedItem>
    <recommendedItem id="20090101_1_183"
                     title="Variant Gene Linked to Diabetes Is Carried by 38% of People"
                     score="-0.007"
                     href="