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1.  Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians 
Diabetologia  2011;55(4):981-995.
FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.
All studies published on the association between FTO-rs9939609 (or proxy [r2 > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.
The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10−19), overweight by 1.13-fold/allele (p = 1.0 × 10−11) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10−8). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10−5). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m2 per allele (p = 2.8 × 10−17), WHR by 0.003/allele (p = 1.2 × 10−6), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations.
FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
PMCID: PMC3296006  PMID: 22109280
Asians; FTO; Meta-analysis; Obesity; Type 2 diabetes
3.  Aldose reductase gene is associated with diabetic macroangiopathy in Japanese Type 2 diabetic patients 
Diabetic Medicine   2006;23(8):894-899.
The aldose reductase (AR) gene, a rate-limiting enzyme of the polyol pathway, has been investigated as a candidate gene in determining susceptibility to diabetic microangiopathy. However, the association of the AR gene with diabetic macroangiopathy has not been investigated. Therefore, the present study was conducted to determine whether genetic variations of AR may determine susceptibility to diabetic macroangiopathy.
There were 378 Type 2 diabetic patients enrolled in this study. A single nucleotide polymorphism in the promoter region (C-106T) was genotyped and the AR protein content of erythrocytes measured by ELISA.
There were no significant differences in genotypic or allelic distribution in patients with or without ischaemic heart diseases, but there was a significant increase in the frequency of the CT + TT genotype and T allele in patients with stroke (P = 0.019 and P = 0.012). The erythrocyte AR protein content was increased in patients with the CT and TT genotype compared with those with the CC genotype. After adjustment for age, duration of diabetes, body mass index, systolic blood pressure, HbA1c, and serum creatinine, triglycerides, and total cholesterol in multivariate logistic-regression models, the association between this AR genotype and stroke remained significant.
Our results suggest that the CT or TT genotype of the AR gene might be a genetic marker of susceptibility to stroke in Type 2 diabetic patients. This observation might contribute to the development of strategies for the prevention of stroke in Type 2 diabetic patients.
PMCID: PMC1619898  PMID: 16911628
aldose reductase; atherosclerosis; macroangiopathy; polymorphism; stroke

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