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Investigating the science of body weight regulation

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Here a SNP, There a SNP

Posted by Miriam Gordon on October 8, 2008

A “SNP” is a single nucleotide polymorphism. Within a genetically distinct population, i.e. people of a certain ethnicity, religion, or geographic region, there are several versions of the DNA sequence of any given gene that is almost identical, with the exception of one sequence unit at a specific site. This single nucleotide variation occurs in the population at observable frequencies. The Human Genome Project, a multinational collaboration to sequence the entire human genome (the DNA sequence in all 23 human chromosomes), opened the door to the discovery of many of these SNPs, which were present in genes thought to be very important in disease risk. The differences created by a SNP in a gene could give rise to a protein that could either increase or decrease the risk of getting a disease. Establishing the correlation of the frequency of occurrence of a SNP with the risk of getting a specific disease could lead to improvements in the health of an individual at risk, either by recommending specific therapies or changes in lifestyle or diet.

In a ground-breaking study entitled “Variants of the Adiponectin (ADIPOQ) and Adiponectin Receptor 1 (ADIPOR1) Genes and Colon Cancer Risk” (JAMA. 2008 Oct 1;300(13):1523-31), Virginia G. Kaklamani et al found a statistically significant correlation of a SNP in the ADIPOQ gene with incidence of colon cancer in a large cohort of subjects with Ashkenazi Jewish ancestry. This work is ground-breaking because it is the first published study to establish a real statistical correlation of a SNP based variant of the adiponectin gene with the incidence of colon cancer, after many circumstantial, indirect observations. Ironically, the SNP in the ADIPOQ gene was negatively correlated with colon cancer risk. In other words, individuals with the SNP containing GG or GC (found in 48% of all study participants) at the variant site were 27% less likely to develop colon cancer than those with the more common CC genotype. It is very important to remember, however, that as the authors caution, these results must be confirmed with further studies.

Adiponectin is an adipokine, or a hormone secreted by adipose tissue, that facilitates insulin sensitivity. Paradoxically, as adipose tissue mass increases, adiponectin levels decrease, and this is correlated with insulin resistance. Insulin resistance is correlated with elevated levels of other proteins, such as C-peptide and insulin-like growth factor binding protein-1 (IGFBP1) that is linked to increased risk of colon cancer. The results of this study suggest that there may be some identifiable genetic and biochemical connections between obesity, diabetes, and colon cancer.

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