Genetic Effects of FTO and MC4R Polymorphisms on Body Mass in Constitutional Types

Seongwon Cha,Jong Y Kim,Sun M Choi,Hyoung D Shin,Sangkyun Jeong,Imhoi Koo,Byung L Park,Kil S Kim

doi:10.1093/ecam/nep162

Abstract

Sasang constitutional medicine (SCM), a Korean tailored medicine, categorizes human beings into four types through states of physiological imbalances and responsiveness to herbal medicine. One SCM type susceptible to obesity seems sensitive to energy intake due to an imbalance toward preserving energy. Common variants of fat mass and obesity associated (FTO) and melanocortin 4 receptor (MC4R) genes have been associated with increased body mass index (BMI) by affecting energy intake. Here, we statistically examined the association of FTO and MC4R polymorphisms with BMI in two populations with 1370 Koreans before and after SCM typing, and with the lowering of BMI in 538 individuals who underwent a 1-month lifestyle intervention. The increased BMI replicated the association with FTO haplotypes (effect size ≃ 1.1 kg/m2) and MC4R variants (effect size ≃ 0.64 kg/m2). After the lifestyle intervention, the carriers of the haplotype represented by the minor allele of rs1075440 had a tendency to lose more waist-to-hip ratio (0.76%) than non-carriers. The constitutional discrepancy for the accumulation of body mass by the effects of FTO and/or MC4R variants seemed to reflect the physique differences shown in each group of SCM constitutional types. In conclusion, FTO and MC4R polymorphisms appear to play an important role in weight gain, while only FTO variants play a role in weight loss after lifestyle intervention. Different trends were observed among individuals of SCM types, especially for weight gain. Therefore, classification of individuals based on physiological imbalance would offer a good genetic stratification system in assessing the effects of obesity genes.

Highlights

Common variations in the first intron of the fat mass and obesity associated (FTO) gene, have been shown to be risk factors for obesity in several studies of Caucasian [1,2,3], Asian [4,5,6,7,8,9] and African American [10] subjects
Consistent with previous studies, we replicated the association of melanocortin 4 receptor (MC4R) with body mass index (BMI) in a Korean population for the first time and we confirmed the association of the FTO Linkage disequilibrium (LD) block with obesity-related phenotypes in Koreans
Our findings revealed that the haplotypes represented by minor alleles of three single nucleotide polymorphism (SNPs) located within the first intron of FTO were associated with body mass (Supplementary Tables 2 and 5)

Summary

Introduction

Common variations in the first intron of the fat mass and obesity associated (FTO) gene, have been shown to be risk factors for obesity in several studies of Caucasian [1,2,3], Asian [4,5,6,7,8,9] and African American [10] subjects. Conflicting results have been generated in certain Asian (e.g., Japanese and Chinese) [11, 12] and African American [3] populations These inconsistencies may stem from certain genetic or non-genetic factors that were not taken into account by the study authors [13]. For these reasons, we became interested in a traditional Korean medicine approach that uses constitutional typing and novel stratification criteria to assess the risk factors for obesity in humans with different genetic compositions. It may be possible to achieve more delicate and stringent analyses of the risk factors for obesity via the stratification of populations according to SCM typing

Methods

Results

Conclusion