New Findings for Specific Human Genetic Variants and the Risk for Obesity

New Findings for Specific Human Genetic Variants and the Risk for Obesity

japanA study from researchers in Japan entitled “Seasonal effects of the UCP3 and the RPTOR gene polymorphisms on obesity traits in Japanese adults”, analyzed the possible link between specific human genetic variations and the tendency for obesity. The study was published in the Journal of Physiological Anthropology.

Non-shivering thermogenesis (NST) is defined as a heat production mechanism induced by cold that is not linked to muscle shivering. NST requires considerable energy costs to the human body and is for this reason considered a contributing factor to the reduction of the obesity risk.

A single nucleotide polymorphism (SNP) corresponds to a DNA sequence variation within a population, for instance, when a single nucleotide in the genome differs between members of the same species. SNPs have been reported in molecular evolutionary genetic studies to be present in or near two genes that might influence NST – uncoupling protein 3 gene (UCP3) and regulatory associated protein of mTOR complex 1 gene (RPTOR). These SNPs were suggested to be relevant for thermogenic mechanisms in mammals and to confer an adaptive advantage to humans that allowed us in the past to disperse and support cold environments. It was also suggested that such SNPs could therefore contribute to the susceptibility to obesity.

One such case has been reported, in which a SNP near the UCP1 gene (uncoupling protein 1) proved to be a genetic variation linked to cold adaptation and resistance to obesity in humans. This SNP was curiously more prevalent in ethnic groups inhabiting higher latitudes.

In order to determine if this was also the case for UCP3 and RPTOR genes, the team investigated the impact of the specific SNPs in obesity-related traits in modern humans using a large-scale cohort. 2,834 Japanese adults (46% female; mean age of 51.5) were selected from a population of individuals who attended the Jichi Medical University Healthcare Center during January 2009 to March 2011for general health checkups. The individuals were assessed regarding the possible link between two genetic variations in the UCP3 and RPTOR genes (SNPs: UCP3-55C/T and RPTOR-26934C/T) and obesity-related traits.

The results showed that the two SNPs in UCP3 and RPTOR genes were not associated with any of the obesity traits analyzed, namely body mass index (BMI), waist circumference, visceral fat area (VFA) and VFA adjusted for BMI, or the blood chemical parameters measured (hemoglobin, fasting plasma glucose, plasma triglycerides, total cholesterol and high-density lipoprotein cholesterol). Seasonality influences VFA, so the seasonal effects of the two SNPs were also evaluated, but it was concluded that there was also no significant association between the SNPs and obesity traits.

The authors concluded that the two genetic variations in UCP3 and RPTOR genes did not influence obesity-related traits and that the effects of these two SNPs on energy metabolism balance may be subtle. The authors propose that the climate-associated natural selection observed for the SNPs of UCP3 and RPTOR could possibly be explained by other physiological functions besides NST, and that this requires further studies. Other SNPs in the two genes analyzed were also reported to putatively influence obesity-related traits, and they too require further investigation.

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