Tabara, Y. et al. Prognostic significance of FTO genotype in the development of obesity in Japanese: the J-SHIPP study. Int. J. Obes. doi:10.1038/ijo.2009.161

FTO (fat mass and obesity-associated) genotype is an independent risk factor for the future development of obesity, a longitudinal, retrospective study from Japan has shown.

Cross-sectional associations between a variant of the FTO gene (rs9939609) and obesity have been reported in populations with European ancestry as well as other populations including the Japanese. Nevertheless, cross-sectional data do not shed light on the prognostic significance of the FTO genotype and insufficient longitudinal data exist to draw firm conclusions about the future obesity risk conferred by variation within the FTO loci.

The Japanese team had a public health aim for their study. “In order to identify people genetically at-risk for obesity, we wanted to clarify whether the genetic variation in FTO is independently associated with future development of obesity,” says lead study author Yasuharu Tabara of Ehime University Graduate School of Medicine, Ehime, Japan.

In European populations, the melanocortin 4 receptor (MC4R) variant rs17782313 is another obesity-associated allele. Both the FTO and the MC4R variant are believed to affect susceptibility to obesity by modulating an individual's energy intake and food choices; energy expenditure does not seem to be affected. Tabara and co-investigators genotyped both FTO rs9939609 and MC4R rs17782313 in 2,806 community-dwelling, middle-aged to elderly Western Japanese individuals (mean age 61±14 years). The researchers analyzed retrospective health data of the participants, which was available for 2,273 of the cohort.

The findings of the cross-sectional analysis revealed a similar association between the FTO variant rs9939609 and obesity to that reported previously in Japanese populations. After adjustment for age and sex, the odds ratio for obesity was twice as high in individuals with the AA genotype (A is the risk allele) as it was for those with the TT genotype. Interestingly, no significant association was found between the MC4R genotype and BMI or obesity frequency. Thus, the susceptibility to obesity associated with the MC4R allele rs17782313 found in European populations may not also apply to Japanese populations.

In the retrospective study, which had a mean follow up of 9.4 years, 214 new cases of obesity (BMI ≥25 kg/m2; in accordance with guidelines of the Japanese Society for the Study of Obesity) were diagnosed amongst 1,718 participants who were not obese at baseline. Frequency of FTO risk-alleles amongst these newly obese participants was significantly higher than amongst the 1,504 participants who did not develop obesity. Notably, the FTO genotype remained an independent risk factor for the development of obesity after adjustment for possible confounding factors, including initial BMI, age and sex. The prognostic significance of the FTO genotype seemed to be particular high for the younger members of the cohort—the middle aged rather than the elderly.

Obesity prevention is an important pubic health mission, and the findings of this Japanese team could provide useful insights. “Since body weight is a trait that is modifiable by dietary and exercise interventions,” reasons Tabara. “Early detection of at-risk populations using genetic information may be useful in preventing future development of obesity and obesity-related diseases.”