Genetics of obesity
Like many other medical conditions, obesity is the result of an interplay between genetic and environmental factors. Polymorphisms in various genes controlling appetite and metabolism predispose to obesity under certain dietary conditions. The percentage of obesity that can be attributed to genetics varies widely, depending on the population examined, from 6% to 85%. As of 2006, more than 41 sites on the human genome have been linked to the development of obesity when a favorable environment is present. The involvement of genetic factors in the development of obesity is estimated to be 40–70%. Some of these obesogenic or leptogenic genes may influence obese individuals response to weight loss or weight management.
Confirmed and hypothesized associations include:
|leptin receptor deficiency||601007||1p31|
|prohormone convertase-1 deficiency||600955||5q15-q21|
|melanocortin-4 receptor polymorphism (MC4R)||155541||18q22|
|BMIQ3||6q23-q25||near D6S1009, GATA184A08, D6S2436, and D6S305|
|BMIQ4||11q24||near D11S1998, D11S4464, and D11S912|
|FTO||16q12.2||Adults who were homozygous for a particular FTO allele weighed about 3 kilograms more and had a 1.6-fold greater rate of obesity than those who had not inherited this trait. This association disappeared, though, when those with FTO polymorphisms participated in moderately intensive physical activity equivalent to three to four hours of brisk walking.|
|KCTD15||19q13.12||KCTD15 plays a role in transcriptional repression of AP-2α, which in turn, inhibits the activity of C/EBPα, an early inducer of adipogenesis.|
Some studies have focused upon inheritance patterns without focusing upon specific genes. One study found that 80% of the offspring of two obese parents were obese, in contrast to less than 10% of the offspring of two parents who were of normal weight.
The thrifty gene hypothesis postulates that due to dietary scarcity during human evolution people are prone to obesity. Their ability to take advantage of rare periods of abundance by storing energy as fat would be advantageous during times of varying food availability, and individuals with greater adipose reserves would more likely survive famine. This tendency to store fat, however, would be maladaptive in societies with stable food supplies. This is the presumed reason that Pima Indians, who evolved in a desert ecosystem, developed some of the highest rates of obesity when exposed to a Western lifestyle.
Numerous studies of laboratory rodents provide strong evidence that genetics plays an important role in obesity.
The risk of obesity is determined by not only specific genotypes but also gene-gene interactions. However, there are still challenges associating with detecting gene-gene interactions for obesity.
Obesity is also a major feature in several syndromes, such as Prader-Willi syndrome, Bardet-Biedl syndrome, Cohen syndrome, Ayazi syndrome, and MOMO syndrome. (The term "non-syndromic obesity" is sometimes used to exclude these conditions.) In people with early-onset severe obesity (defined by an onset before 10 years of age and body mass index over three standard deviations above normal), 7% harbor a single locus mutation.
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