Common FTO rs9939609 variant and risk of type 2 diabetes in Palestine

Sabarneh, Anas; Ereqat, Suheir; Cauchi, Stéphane; AbuShamma, Omar; Abdelhafez, Mohammad; Ibrahim, Michella; Nasereddin, Abedelmajeed

doi:10.1186/s12881-018-0668-8

Cited by 27 publications

(13 citation statements)

References 41 publications

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“…Furthermore, the increased expression of m 6 A methylation upregulates the insulin/insulin-like growth factor 1 (IGF1)-AKT-pancreatic and duodenal homeobox 1 (PDX1) pathway by targeting METTL14 or METTL3 in human β-cells, which ultimately inhibits cell-cycle arrest and protects insulin secretion [71]. Besides, single nucleotide polymorphisms (SNPs) in FTO are also strongly associated with T2D, such as variant rs9939609 and rs17817449 of FTO gene [72], which are important for the development of insulin resistance and occurrence of T2D [73]. Together, m 6 A modulators might be potential therapeutic targets for maintaining…”

Section: Mettl14mentioning

confidence: 99%

RNA N6-methyladenosine: a promising molecular target in metabolic diseases

Wang

Huang

et al. 2020

Cell Biosci

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N6-methyladenosine is a prevalent and abundant transcriptome modification, and its methylation regulates the various aspects of RNAs, including transcription, translation, processing and metabolism. The methylation of N6-methyladenosine is highly associated with numerous cellular processes, which plays important roles in the development of physiological process and diseases. The high prevalence of metabolic diseases poses a serious threat to human health, but its pathological mechanisms remain poorly understood. Recent studies have reported that the progression of metabolic diseases is closely related to the expression of RNA N6-methyladenosine modification. In this review, we aim to summarize the biological and clinical significance of RNA N6-methyladenosine modification in metabolic diseases, including obesity, type 2 diabetes, non-alcoholic fatty liver disease, hypertension, cardiovascular diseases, osteoporosis and immune-related metabolic diseases.

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Section: Mettl14mentioning

confidence: 99%

RNA N6-methyladenosine: a promising molecular target in metabolic diseases

Wang

Huang

et al. 2020

Cell Biosci

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“…The fat mass and obesity-associated (FTO) gene [chromosome 16 (16q12.2a)] has shown the largest effect on BMI, although the increase is modest [7]. The link of FTO rs9939609 allele to high BMI was described in many previous studies all over the world [8,9] and in the Middle East; including Saudi Arabians [10], Kuwaitis [11], Emiratis [12] and diabetic Palestinians [13]. It has been also identified as a genetic risk of metabolic syndrome in Egyptians [14].…”

Section: Introductionmentioning

confidence: 99%

The FTO genetic variants are associated with dietary intake and body mass index amongst Emirati population

et al. 2019

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BackgroundThe risk of obesity is determined by complex interactions between genetic and environmental factors. Little research to date has investigated the interaction between gene and food intake. The aim of the current study is to explore the potential effect of fat mass and obesity-associated protein gene (FTO) rs9939609 and rs9930506 single nucleotide polymorphism (SNP) on the pattern of food intake in the Emirati population.MethodsAdult healthy Emirati subjects with Body mass index (BMI) of 16–40 kg/m2 were included in the study. Genotyping for FTO rs9939609() and rs9930506() was performed using DNA from saliva samples. Subjects were categorized according to the WHO classification by calculating the BMI to compare different classes. Dietary intake was assessed by a sixty-one-item FFQ that estimated food and beverage intakes over the past year. The daily energy, macronutrient, and micronutrient consumption were computed.ResultsWe included 169 subjects in the final analysis (mean age 30.49± 9.1years, 57.4% females). The mean BMI of the study population was 26.19 kg/m2. Both SNPs were in Hardy Weinberg Equilibrium. The rs9939609 genotype was significantly associated with higher BMI (p = 0.004); the effect was significant in females (p = 0.028), but not in males (p = 0.184). Carbohydrate intake was significantly higher in subjects with a trend of lower fat intake compared to other genotypes. The odds ratio for the was 3.78 in the fourth quartile and 2.67 for the in the second quartile of total carbohydrate intake, considering the first quartile as a reference (95% CI = 1.017–14.1 and 1.03–6.88, respectively). Fat intake was significantly lower in the FTO rs9930506 subjects. The presence of FTO rs9930506 genotype decreased the fat intake in subjects with FTO rs9939609 (p = 0.037).ConclusionsThe results of this study highlight the interaction of the FTO risk alleles on the food intake in Emirati subjects. The FTO rs9939609 subjects had higher carbohydrate and lower fat intake. The latter was accentuated in presence of rs9930506 genotype.

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“…Blood pressure was measured in sitting position, on the left arm, after a 5-min rest by a health clinic worker, with a mercury sphygmomanometer. Blood samples (five ml) after a 12-h minimum fast was collected in EDTA tubes for biochemical tests as described in our previous work (Sabarneh et al, 2018). Plasma glucose, cholesterol, HDL cholesterol, and triglyceride were determined using standard methods of commercial kits (Human, Wiesbaden, Germany).…”

Section: Methodsmentioning

confidence: 99%

Estrogen receptor 1 gene polymorphisms (PvuII and XbaI) are associated with type 2 diabetes in Palestinian women

Ereqat

Cauchi

Eweidat

et al. 2019

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Background Type 2 diabetes mellitus (T2DM) is a multifactorial disease where both genetic and environmental factors contribute to its pathogenesis. The PvuII and XbaI polymorphisms of the estrogen receptor 1 (ESR1) gene have been variably associated with T2DM in several populations. This association has not been studied in the Palestinian population. Therefore, the aim of this study was to investigate the association between the PvuII and XbaI variants in the ESR1 and T2DM and its related metabolic traits among Palestinian women. Methods This case–control study included 102 T2DM and 112 controls in which PvuII and XbaI variants of the ESR1 gene were genotyped using amplicon based next generation sequencing (NGS). Results Allele frequencies of both PvuII and XbaI variants were not significantly different between patients and control subjects (P > 0.05). In logestic regression analysis adjusted for age and BMI, the ESR1 PvuII variant was associated with risk of T2DM in three genotypic models (P < 0.025) but the strongest association was observed under over-dominant model (TT+CC vs. TC) (OR = 2.32, CI [1.18–4.55] adjusted P = 0.013). A similar but non-significant trend was also observed for the ESR1 XbaI variant under the over-dominant model (AA+GG vs. AG) (OR = 2.03, CI [1.05–3.95]; adjusted P = 0.035). The frequencies of the four haplotypes (TA, CG, CA, TG) were not significantly different in the T2DM patients compared with control group (P > 0.025). Among diabetic group, an inverse trend with risk of cardio vascular diseases was shown in carriers of CG haplotype compared to those with TA haplotype (OR = 0.28, CI [0.09–0.90]; adjusted P = 0.035). Further, stratified analyses based on ESR1 PvuII and XbaI genotypes revealed no evidence for association with lipid levels (TC, TG, HDL, LDL). Conclusions This is the first Palestinian study to conclude that ESR1 PuvII and XbaI variants may contribute to diabetes susceptibility in Palestinian women. Identification of genetic risk markers can be used in defining high risk subjects and in prevention trials.

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Common FTO rs9939609 variant and risk of type 2 diabetes in Palestine

Cited by 27 publications

References 41 publications

RNA N6-methyladenosine: a promising molecular target in metabolic diseases

RNA N6-methyladenosine: a promising molecular target in metabolic diseases

The FTO genetic variants are associated with dietary intake and body mass index amongst Emirati population

Estrogen receptor 1 gene polymorphisms (PvuII and XbaI) are associated with type 2 diabetes in Palestinian women

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