FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians

Yajnik, Chittaranjan S; Janipalli, C. S.; Bhaskar, Suryanarayanan; Kulkarni, S. R.; Freathy, Rachel M.; Prakash, Swami; Mani, K. Radha; Weedon, Michael N.; Kale, S. D.; Deshpande, Jaya; Krishnaveni, Ghattu V.; Veena, Sargoor R.; Fall, Caroline H.D.; McCarthy, Mark I.; Frayling, Timothy M.; Hattersley, Andrew T.; Chandak, Giriraj Ratan

doi:10.1007/s00125-008-1186-6

Cited by 166 publications

(159 citation statements)

References 36 publications

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“…Newly identified variants of the FTO gene have been associated with obesity in large cohorts worldwide (1-6), whereas its association with T2D was of lower magnitude (7)(8)(9)(10). However, the function of FTO and its role in human obesity and T2D remains to be defined.…”

Section: Discussionmentioning

confidence: 99%

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The expression of FTO in human adipose tissue is influenced by fat depot, adiposity, and insulin sensitivity

Bravard

Veilleux

Disse

et al. 2013

Obesity

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Objective: The fat mass and obesity associated (FTO) gene is related to obesity, but the regulation of FTO expression in adipose tissue is not fully understood. We investigated FTO expression in paired subcutaneous and omental adipose tissues (SAT and OAT) from healthy women undergoing gynecological surgeries, and its relation with adiposity and insulin sensitivity. Design and Methods: FTO expression in SAT of type 2 diabetic patients treated or not with Rosiglitazone was also compared. Results: Both the mRNA and protein levels of FTO were higher in OAT from women than in SAT. Only OAT FTO protein levels negatively correlated with BMI and body fat mass, whereas SAT FTO mRNA levels were negatively correlated with subcutaneous fat deposition. In addition, SAT FTO mRNA and protein levels were increased in insulin resistant women (high HOMA) compared to insulin sensitive women (low HOMA), whereas OAT FTO expression was not different between these two subgroups. Interestingly, FTO mRNA levels were increased in SAT of type 2 diabetic patients, and treatment of diabetics with Rosiglitazone improved insulin sensitivity and reduced SAT FTO mRNA levels. Lastly, FTO expression was transiently increased in the early phase of 3T3-L1 cell differentiation, which coincides with the induction of PPARc2 expression. However, partial reduction of FTO did not impact PPARc2 expression and adipocyte differentiation. Conclusion: Therefore, FTO gene expression is higher in OAT than in SAT in lean to moderately obese women. OAT FTO expression is associated with adiposity, whereas SAT FTO expression is associated with insulin sensitivity. These associations are independent of an effect of FTO on adipocyte differentiation.

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Section: Discussionmentioning

confidence: 99%

“…Variants have also been associated with type 2 diabetes (T2D) independently of BMI in other cohorts of various ethnic backgrounds (7)(8)(9)(10). We are still at an early stage in our understanding of the pathways through which FTO confers increased obesity and T2D risk.…”

Section: Introductionmentioning

confidence: 99%

The expression of FTO in human adipose tissue is influenced by fat depot, adiposity, and insulin sensitivity

Bravard

Veilleux

Disse

et al. 2013

Obesity

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“…One of these genetic variants (rs9939609), located within the first FTO intron, has been related to an increased risk for both obesity and type 2 diabetes mellitus (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Although the association of the FTO gene with obesity is observed across many different ethnic populations (7)(8)(9)(10)(11)(12)(13)(14)(15)(16), there are several controversies. Some showed an association of the FTO gene with obesity (15)(16), and some failed to replicate the result (17).…”

Section: Introductionmentioning

confidence: 99%

Association of the rs9939609 gene variant in FTO with insulin resistance, carciovascular risk factor and serum adipokine levels in obese patients

et al. 2016

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“…2 Genetic factors are considered to contribute to the high prevalence of diabetes. 3 However, the fetal origins hypothesis has also been put forward to explain the vulnerability of South Asian individuals to diabetes. A central theme of this hypothesis is that adaptive changes in metabolicendocrine pathways are necessary for a malnourished fetus to survive.…”

Section: Introductionmentioning

confidence: 99%

Neonatal anthropometry: thin–fat phenotype in fourth to fifth generation South Asian neonates in Surinam

Steijn

Karamali²,

Kanhai

et al. 2009

Int J Obes

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We assessed whether the earlier described 'thin-fat phenotype' is present in Surinam South Asian babies of the fourth to fifth generation after migration from India. In this observational study we collected data from 39 South Asian term neonates and their mothers in Paramaribo, Surinam. We compared the following data with data from an earlier study in Southampton, UK (338 neonates) and in Pune, India (631 neonates): maternal body mass index, neonatal weight, length, head, mid-upper arm and abdominal circumferences and subscapular skinfold thickness. The mothers in Paramaribo were older than the Southampton mothers; their body mass index was comparable. Mean birth weight was 3159 g (Southampton: 3494 g; Pune: 2666 g). Compared with Southampton babies, the Paramaribo babies were smaller in nearly all body measurements, the smallest being abdominal circumference at the umbilicus level (s.d. score: À1.62; 95% confidence interval (CI): À2.07 to À1.16) and midupper arm circumference (s.d. score: À1.08; 95% CI: À1.46 to À0.69). In contrast, subscapular skinfold thickness was similar (s.d. score: þ 0.08; 95% CI: À0.24 to þ 0.55). Except for subscapular skinfold thickness and length, all neonatal measurements were intermediate between those from Southampton and Pune. The thin-fat phenotype is preserved in Surinam South Asian neonates of the fourth to fifth generation after migration from India.

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FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians

Cited by 166 publications

References 36 publications

The expression of FTO in human adipose tissue is influenced by fat depot, adiposity, and insulin sensitivity

The expression of FTO in human adipose tissue is influenced by fat depot, adiposity, and insulin sensitivity

Association of the rs9939609 gene variant in FTO with insulin resistance, carciovascular risk factor and serum adipokine levels in obese patients

Neonatal anthropometry: thin–fat phenotype in fourth to fifth generation South Asian neonates in Surinam

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