FTO variants are associated with obesity in the Chinese and Malay populations in Singapore.
OBJECTIVE
Association between genetic variants at the FTO locus and obesity has been consistently observed in populations of European ancestry and inconsistently in non-Europeans. The aim of this study was to examine the effects of FTO variants on obesity and type 2 diabetes in Southeast Asian populations.


METHODS
We examined associations between nine previously reported FTO single nucleotide polymorphisms (SNPs) with obesity, type 2 diabetes, and related traits in 4,298 participants (2,919 Chinese, 785 Malays, and 594 Asian Indians) from the 1998 Singapore National Health Survey (NHS98) and 2,996 Malays from the Singapore Malay Eye Study (SiMES).


RESULTS
All nine SNPs exhibited strong linkage disequilibrium (r(2) = 0.6-0.99), and minor alleles were associated with obesity in the same direction as previous studies with effect sizes ranging from 0.42 to 0.68 kg/m(2) (P < 0.0001) in NHS98 Chinese, 0.65 to 0.91 kg/m(2) (P < 0.02) in NHS98 Malays, and 0.52 to 0.64 kg/m(2) (P < 0.0001) in SiMES Malays after adjustment for age, sex, smoking, alcohol consumption, and exercise. The variants were also associated with type 2 diabetes, though not after adjustment for BMI (with the exception of the SiMES Malays: odds ratio 1.17-1.22; P </= 0.026).


CONCLUSIONS
FTO variants common among European populations are associated with obesity in ethnic Chinese and Malays in Singapore. Our data do not support the hypothesis that differences in allele frequency or genetic architecture underlie the lack of association observed in some populations of Asian ancestry. Examination of gene-environment interactions involving variants at this locus may provide further insights into the role of FTO in the pathogenesis of human obesity and diabetes.
Tan
Jonathan T
JT
Center for Molecular Epidemiology, National University of Singapore, Singapore, Singapore.
Dorajoo
Rajkumar
R
Seielstad
Mark
M
Sim
Xue Ling
XL
Ong
Rick Twee-Hee
RT
Chia
Kee Seng
KS
Wong
Tien Yin
TY
Saw
Seang Mei
SM
Chew
Suok Kai
SK
Aung
Tin
T
Tai
E-Shyong
ES
D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012846:Singapore
D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human