Genetic variants linked to severe obesity

By Jimmy Downs

A new study suggests that obese people likely have some genetic alternations in certain genes or certain key segments of DNA that either drive them to eat more than they need or use food in different ways.

The study published in the Dec 6 2009 issue of Nature, the prestigious scientific journal, found the loss of a key segment of DNA is linked to severe childhood obesity.

Dr Sadaf Farooqi from the University of Cambridge and Dr Matt Hurles from the Wellcome Trust Sanger Institute scanned genomes of 300 children with severe obesity and 7,000 control for types of mutation known as copy number variants (CNVs).

CNVs, multiple genes that are either duplicated or deleted from our DNA, are believed to play an important role in some complex diseases like autism and learning disabilities.

The researchers found that certain parts of the genome were missing in some children with severe obesity. Specifically, Dr. Farooqi was cited as saying that children with part of chromosome 16 deleted have severe obesity in their childhood or at a young age.

One particular gene on chromosome 16 known as SH2B1 is involved in regulating weight and handling blood sugar levels and people with this gene missing have a strong crave to eat and gain weight very easily, Dr. Farcooqi said.

Dr. Matt Hurdles said "this is the first evidence that copy number variants have been linked to a metabolic condition such as obesity."

But this study is not the first to associate copy number variants with obesity.

Dr. Bao-Yong Sha and colleagues from Xian Jiaotong University, Hunan Normal University and the University of Missouri published a study report online Feb 20, 2009 in Journal of Human Genetics saying that they found one CNV at 10q11.22 was associated with body mass index.

According to the authors, this CNS contributed 1.6 percent of BMI variation and it covers one important obesity gene known as pancreatic polypeptide receptor (PPYR1), which was discovered earlier.

For the study, Dr. Sha and colleagues performed genome-wide genotyping in 597 elderly Chinese Han subjects, 258 males and 339 females, to locate CNVs in the subjects.

The researchers selected 24 out of 1395 CNVs for analysis of association between BMI and CNVs and they found one  was associated with BMI with nominal significant.

Sha et. al wrote" Association analysis showed that the CNV 10q11.22 loss was significantly associated with higher BMI. Compared with the 567 subjects with two gene copy numbers (normal diploid), subjects with CNV 10q11.22 loss had 12.4% higher BMI value, and subjects with CNV 10q11.22 gain had 5.4% lower BMI value."

Genome-wide association analysis suggests that certain genes play an important role in obesity. But genes are not the only determinant for obesity risk.

Epidemiological studies have suggested that increased intake of energy and reduced consumption of high-fiber foods as well as sedentary lifestyle are the major driving forces for obesity, said Lu Qi and Young Ae Cho at Harvard School of Public Health in a review article published in the Nov 19. 2008 issue of Nutrition Reviews.

For more information on CNVs, read http://en.wikipedia.org/wiki/Copy_number_variation