Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

Apalasamy, Yamunah Devi; Mao, Ming; Rampal, Sanjay; Bulgiba, Awang; Mohamed, Zahurin

doi:10.1590/s0100-879x2012007500134

Cited by 19 publications

(16 citation statements)

References 32 publications

(44 reference statements)

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“…The FTO gene is located on chromosome 16, position 16q12.2, and comprises 9 exons. This gene is expressed in the hypothalamus, at the level of the arcuate nucleus, which is responsible for appetite behavior and fatty acid metabolism, among others ( 24 , 25 ). Therefore, a recent cross-sectional study was performed on 406 Brazilian children and adolescents aged 7–17 years, among whom 34.5% were overweight or obese.…”

Section: Fat Mass and Obesity-associated (Fto) Gene And Obesitymentioning

confidence: 99%

New Insights Regarding Genetic Aspects of Childhood Obesity: A Minireview

Mărginean

Meliţ

2018

Front. Pediatr.

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Introduction: Childhood obesity is occurring at alarming rates in both developed and developing countries. “Obesogenic” environmental factors must be associated with variants of different risk alleles to determine polygenic or common obesity, and their impact depends on different developmental stages.The interaction between obesogenic environment and genetic susceptibility results in the so-called polygenic forms of obesity. In contrast, monogenic and syndromic obesity are not influenced by environmental events. Therefore, this review aimed to underline the roles of some of the most studied genes in the development of monogenic and polygenic obesity in children.Results: Among the most common obesity related genes, we chose the fat mass and obesity-associated (FTO) gene, leptin gene and its receptor, tumor necrosis factor alpha (TNF-α), the melanocortin 4 receptor gene (MC4R), Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1), and others, such as peroxisome proliferator-activated receptor gamma (PPARG), angiotensin-converting enzyme (ACE), glutathione S-transferase (GST), and interleukin-6 (IL-6) genes. The roles of these genes are complex and interdependent, being linked to different cornerstones in obesity development, such as appetite behavior, control of food intake and energy balance, insulin signaling, lipid and glucose metabolism, metabolic disorders, adipocyte differentiation, and so on.Conclusions: Genetic predisposition is mandatory, but not enough to trigger obesity.Dietary interventions and proper lifestyle changes can prevent obesity development in genetically predisposed children. Further studies are needed to identify the precise role of both genetic and obesogenic factors in the development of childhood obesity in order to design effective preventive methods.

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Section: Fat Mass and Obesity-associated (Fto) Gene And Obesitymentioning

confidence: 99%

New Insights Regarding Genetic Aspects of Childhood Obesity: A Minireview

Mărginean

Meliţ

2018

Front. Pediatr.

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“…In the Malaysian population, two studies reported associations between candidate gene polymorphisms and blood lipids in adults [15,16], while only one study on dietary patterns [17]. Hence, gene-diet interaction studies involving candidate genes and dietary patterns on risk factors of CVD such as hyperlipidemia and hypercholesterolemia are scarce in the Malaysian population.…”

Section: Introductionmentioning

confidence: 99%

Association and Interaction Effect between VEGF Receptor-2 (VEGFR-2) Gene Polymorphisms and Dietary Pattern on Blood Lipids in Malaysian Adults

Yap¹,

Masaki²,

Shidoji³

et al. 2014

J. Nutr. Ther.

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Background: Vascular endothelial growth factor receptor-2 (VEGFR-2) and diet are related to blood lipid health. Gene-diet interaction studies can identify the risks. The objectives are to determine associations, and interaction effects between VEGFR-2 gene polymorphisms (rs1870377 and rs2071559) and dietary patterns on blood lipids in multiethnic Malaysian adults. Methods: Dietary intakes of 509 (153 Malay, 179 Chinese, and 177 Indian) Malaysians were obtained from food frequency questionnaire for the construction of dietary patterns using factor analysis. Anthropometric measurements: body mass index and blood pressure; and biomarkers: glycated hemoglobin, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total cholesterol/HDL-C ratio were determined. Genotyping of rs1870377 and rs2071559 was performed by real-time PCR using Taqman probes. Results: Two major dietary patterns were extracted from all subjects: 'Vegetables, fruits, and soy diet' (VFSD), and 'Rice, egg, and fish diet' (REFD). There were significant genetic associations for rs2071559 with TG (p=0.048) in Malays, and in Chinese for rs1870377 with TC (p=0.001) and LDL-C (p=0.007), and rs2071559 on LDL-C (p=0.048). The interaction effects of VEGFR-2 gene polymorphisms and dietary patterns were significant in Malays between rs2071559 and REFD on TG (p=0.005); and in Chinese between VFSD and rs1870377 on LDL-C (p=0.028) after adjusting for potential confounders. There were no significant genetic or dietary associations on blood lipids in Indians (p>0.05). Conclusion: The significant associations and gene-diet interaction effects between VEGFR-2 gene polymorphisms and dietary patterns on blood lipids may pose hyperlipidemia and hypercholesterolemia risks in Malay and Chinese Malaysians.

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“…In addition to body fat distribution traits, rs17817288 was also reported to be associated with predisposition to obesity in multiple populations 13 – 15 . And the associations with the combined samples were mostly contributed by the Caucasian group due to great genetic differentiation 16 .…”

Section: Discussionmentioning

confidence: 99%

Splicing QTL of human adipose-related traits

Jia

Zhao

2018

Sci Rep

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Recently, genome-wide association studies (GWAS) have identified 11 loci associated with adipose-related traits across different populations. However, their functional roles still remain largely unknown. In this study, we aimed to explore the splicing regulation of these GWAS signals in a tissue-specific fashion. For adipose-related GWAS signals, we selected six adipose-related tissues (adipose subcutaneous, artery tibial, blood, heart left ventricle, muscle-skeletal, and thyroid) with the sample size greater than 80 for splicing quantitative trait loci (QTL) analysis using GTEx released datasets. We integrated GWAS summary statistics of nine adipose-related traits (an average of 2.6 million SNPs per GWAS), and splicing QTLs from 6 GTEx tissues with an average of 337,900 splicing QTL SNPs, and 684,859 junctions. Our filtering process generated an average of 86,549 SNPs and 162,841 exon-exon links (junctions) for each tissue. A total of seven exon-exon junctions in four genes (AKTIP, DTNBP1, FTO and UBE2E1) were found to be significantly associated with four SNPs that showed genome-wide significance with body fat distribution (rs17817288, rs7206790, rs11710420 and rs2237199). These splicing events might contribute to the causal effect on the regulation of ectopic-fat, which warrants further experimental validation.

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Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

Cited by 19 publications

References 32 publications

New Insights Regarding Genetic Aspects of Childhood Obesity: A Minireview

New Insights Regarding Genetic Aspects of Childhood Obesity: A Minireview

Association and Interaction Effect between VEGF Receptor-2 (VEGFR-2) Gene Polymorphisms and Dietary Pattern on Blood Lipids in Malaysian Adults

Splicing QTL of human adipose-related traits

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