FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians.
OBJECTIVE
Variants of the FTO (fat mass and obesity associated) gene are associated with obesity and type 2 diabetes in white Europeans, but these associations are not consistent in Asians. A recent study in Asian Indian Sikhs showed an association with type 2 diabetes that did not seem to be mediated through BMI. We studied the association of FTO variants with type 2 diabetes and measures of obesity in South Asian Indians in Pune.


METHODS
We genotyped, by sequencing, two single nucleotide polymorphisms, rs9939609 and rs7191344, in the FTO gene in 1,453 type 2 diabetes patients and 1,361 controls from Pune, Western India and a further 961 population-based individuals from Mysore, South India.


RESULTS
We observed a strong association of the minor allele A at rs9939609 with type 2 diabetes (OR per allele 1.26; 95% CI 1.13-1.40; p = 3 x 10(-5)). The variant was also associated with BMI but this association appeared to be weaker (0.06 SDs; 95% CI 0.01-0.10) than the previously reported effect in Europeans (0.10 SDs; 95% CI 0.09-0.12; heterogeneity p = 0.06). Unlike in the Europeans, the association with type 2 diabetes remained significant after adjusting for BMI (OR per allele for type 2 diabetes 1.21; 95% CI 1.06-1.37; p = 4.0 x 10(-3)), and also for waist circumference and other anthropometric variables.


CONCLUSIONS
Our study replicates the strong association of FTO variants with type 2 diabetes and similar to the study in North Indians Sikhs, shows that this association may not be entirely mediated through BMI. This could imply underlying differences between Indians and Europeans in the mechanisms linking body size with type 2 diabetes.
Yajnik
C S
CS
Diabetes Unit, King Edward Memorial Hospital and Research Centre, Rasta Peth, Pune, India.
Janipalli
C S
CS
Bhaskar
S
S
Kulkarni
S R
SR
Freathy
R M
RM
Prakash
S
S
Mani
K R
KR
Weedon
M N
MN
Kale
S D
SD
Deshpande
J
J
Krishnaveni
G V
GV
Veena
S R
SR
Fall
C H D
CH
McCarthy
M I
MI
Frayling
T M
TM
Hattersley
A T
AT
Chandak
G R
GR
D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D044466:Asian People / Q000706:statistics & numerical data; D001794:Blood Pressure; D015992:Body Mass Index; D016022:Case-Control Studies; D004261:DNA Replication / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005006:Ethnicity / Q000706:statistics & numerical data; D005060:Europe / Q000453:epidemiology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012044:Regression Analysis; D055105:Waist Circumference; D044465:White People / Q000706:statistics & numerical data
D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human