Research Links Two Genes To Obesity And Health Disorders

Family DNA may influence development of Metabolic Syndrome.

Two genes may be linked to obesity and health disorders according to new research by the TOPS Obesity and Metabolic Research Center at the Medical College of Wisconsin. The study of obese individuals from four generations of families shows that hereditary DNA may influence development of Metabolic Syndrome, a cluster of conditions effecting one in five Americans, which dramatically increases the risk for heart disease and diabetes. So far, the TOPS families' DNA samples have made it possible for researchers to query almost one million variations in genes that are associated with whether or not someone develops the Metabolic Syndrome and how the disease surfaces in different people.

Soon to be published in Obesity, the official journal of The Obesity Society, the report reveals evidence of two new genes that significantly impact weight gain. One gene affects the growth and development of newborn infants, as well as regulation of glucose/insulin response, lipid profiles, and body weight in adults. The other gene affects pro-inflammatory pathways, which are precursors of traits of Metabolic Syndrome.

"Our genome-wide survey could lead to the creation of early diagnostic tools for detecting risks for developing obesity, as well as the discovery of drugs targeted specifically to these genes," said Yi (Sherry) Zhang, Ph.D., instructor, Department of Medicine, Human & Molecular Genetics Center at the Medical College of Wisconsin. "This is the first published work of our genome-wide survey, and we expect a series of reports will soon follow to address other aspects of this complex disease," she added.

Zhang and her colleagues from the TOPS Obesity Center have been working to determine the full picture of the genetic makeup that encourages development of Metabolic Syndrome, including body composition, insulin resistance, and circulating blood levels of the hormone leptin, which is exclusively produced by fatty tissue.

"We've all heard such common expressions as, 'You have your mom's eyes,' or 'I developed high blood pressure in my '40s, just like my grandfather," notes Barbara Cady, TOPS President. "When we discuss 'inheritance' like this, we're relating to a question that scientists have been striving to answer for decades: how does our genetic makeup determine our traits? Knowing which genes are detrimental to our health may help researchers develop a strategic plan to treat or even prevent the symptoms that are caused by these genes."

This research is the latest in a series of papers based on the TOPS Obesity and Metabolic Research samples housed at the Medical College of Wisconsin as part of an ongoing partnership.

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Adolescent Obesity Associated With Hearing Loss

Obese adolescents are more likely than their normal-weight counterparts to have hearing loss, according to results of a new study. Findings showed that obese adolescents had increased hearing loss across all frequencies and were almost twice as likely to have unilateral (one-sided) low-frequency hearing loss. The study was recently e-published by The Laryngoscope, a journal published by the American Laryngological, Rhinological and Otological Society.

"This is the first paper to show that obesity is associated with hearing loss in adolescents," said study first author Anil K. Lalwani, MD, professor and vice chair for research, Department of Otolaryngology/Head & Neck Surgery, Columbia University Medical Center.

The study found that obesity in adolescents is associated with sensorineural hearing loss across all frequencies (the frequency range that can be heard by humans); sensorineural hearing loss is caused by damage to the inner-ear hair cells. The highest rates were for low-frequency hearing loss - 15.16 percent of obese adolescents compared with 7.89 percent of non-obese adolescents. People with low-frequency hearing loss cannot hear sounds in frequencies 2,000 Hz and below; they may still hear sounds in the higher frequencies (normal hearing range is from 20 Hz to 20,000 Hz). Often they can still understand human speech well, but may have difficulty hearing in groups or in noisy places.

"These results have several important public health implications," said Dr. Lalwani, who is also an otolaryngologist at NewYork-Presbyterian Hospital/Columbia University Medical Center. "Because previous research found that 80 percent of adolescents with hearing loss were unaware of having hearing difficulty, adolescents with obesity should receive regular hearing screening so they can be treated appropriately to avoid cognitive and behavioral issues."

Although the overall hearing loss among obese adolescents was relatively mild, the almost 2-fold increase in the odds of unilateral low-frequency hearing loss is particularly worrisome. It suggests early, and possibly ongoing, injury to the inner ear that could progress as the obese adolescent becomes an obese adult. Future research is needed on the adverse consequences of this early hearing loss on social development, academic performance, and behavioral and cognitive function.

"Furthermore, hearing loss should be added to the growing list of the negative health consequences of obesity that affect both children and adults - adding to the impetus to reduce obesity among people of all ages," said Dr. Lalwani.

In the United States, nearly 17 percent of children are obese, defined as having a body mass index (BMI) of =95 percentile. (BMI in children is expressed as a percentile; adult BMI is expressed as a number based on weight and height.) Obesity and its associated morbidities have been identified as a risk factor for hearing loss in adults.

The study analyzed data from nearly 1,500 adolescents from the National Health and Nutrition Examination Survey - a large, nationally representative sample of adolescents between the ages of 12 and 19, conducted from 2005 to 2006 by the National Center for Health Statistics of the Centers for Disease Control and Prevention. Participants were interviewed at home, taking into account family medical history, current medical conditions, medication use, household smokers, socioeconomic and demographic factors, and noise-exposure history.

Dr. Lalwani and his colleagues speculate that obesity may directly or indirectly lead to hearing loss. Although additional research is needed to determine the mechanisms involved, they theorize that obesity-induced inflammation may contribute to hearing loss. Low plasma levels of the anti-inflammatory protein adiponectin, which is secreted from adipose tissue, have been found in obese children, and low levels in obese adults have been associated with high-frequency hearing loss (which affects a person's ability to understand speech). Obesity also may contribute indirectly to hearing loss as a result of its comorbidities, including type 2 diabetes, cardiovascular disease, and high cholesterol - all of which have been reported to be associated with loss of peripheral hearing (relating to the outer, middle, and inner ear).

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