Intestinal FABP2 A54T Polymorphism: Association with Insulin Resistance and Obesity in Women

Albala, Cecilia; Santos, José Luís; Cifuentes, Mariana; Villarroel, Ana Claudia; Lera, Lydia; Liberman, Claudio; Ángel, Bárbara; Pérez-Bravo, Francisco

doi:10.1038/oby.2004.42

Cited by 62 publications

(48 citation statements)

References 40 publications

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“…FABP2 plays a key role in absorption and intracellular transport of dietary long-chain fatty acids. Carriers of the Thr54 allele have a twofold greater affinity for long-chain fatty acids than those with the Ala54 allele which supports the role of the FABP2 Ala54Thr polymorphism in the etiology of metabolic disorders, such as insulin resistance [17] .…”

Section: Introductionmentioning

confidence: 72%

Influence of ALA54THR Polymorphism of Fatty Acid Binding Protein 2 on Lifestyle Modification Response in Obese Subjects

Luis¹,

Aller²,

Izaola³

et al. 2006

Ann Nutr Metab

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Background/Aim: It has been found that the expression of fatty acid binding protein 2 (FABP2) mRNA is under dietary control. A G-to-A transition at codon 54 of FABP2 results in an amino acid substitution (from Ala 54 to Thr 54). This polymorphism was associated with high insulin resistance and high fasting insulin concentrations. The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 protein on the response to a lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients. Methods: A population of 69 obese (body mass index >30) nondiabetic outpatients was analyzed in a prospective way. Before and after 3 months of the lifestyle modification program, indirect calorimetry, tetrapolar electrical bioimpedance measurement, blood pressure recording, serial assessment of the nutritional intake (3 days of written food records), and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1,520 kcal; 52% carbohydrates, 25% lipids, and 23% proteins). The exercise program consisted of aerobic exercise for at least three times/week (60 min each). Statistical analysis was performed for combined Ala54/Thr54 and Thr54/Thr54 as a mutant group and wild-type Ala54/Ala54 as second group. Results: The mean age was 45.5 ± 16.7 years, the mean body mass index was 34.1 ± 5.1, and there were 14 males (20.3%) and 55 females (79.7%) with a weight loss of 3.17 ± 3.5 kg (3.5%). Thirty-seven patients (53.6%) had the genotype Ala54/Ala54 (wild-type group) and 32 (46.4%) patients either the genotype Ala54/Thr54 (26 patients, 30.2%) or the genotype Thr54/Thr54 (6 patients, 16.2%). The percentage of responders (weight loss) was similar in both groups (89.2 vs. 90.6%). In the wild-type group, body mass index, weight, fat mass, low-density lipoprotein cholesterol level, and waist circumference decreased, whereas the VO₂ (oxygen consumption) increased. In the mutant group, glucose, body mass index, weight, waist circumference, and systolic blood pressure decreased, and VO₂ increased. No differences were detected between basal values in both groups. Only the leptin levels showed a significant decrease in the wild-type group (23.85%; p < 0.05), with no statistically significant difference in the mutant group (2.59%; NS). Resistin, tumor necrosis factor alpha, interleukin 6, insulin, and C-reactive protein remained without changes in both groups. Conclusions: Weight loss is associated with different changes, depending on the FABP2 genotype. Carriers of the Thr54 allele have a different response than wild-type obese subjects, with a significant decrease of systolic blood pressure and glucose levels in Thr54 carriers and a significant decrease in fat mass, low-density lipoprotein cholesterol, and leptin in wild-type patients.

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Section: Introductionmentioning

confidence: 72%

Influence of ALA54THR Polymorphism of Fatty Acid Binding Protein 2 on Lifestyle Modification Response in Obese Subjects

Luis¹,

Aller²,

Izaola³

et al. 2006

Ann Nutr Metab

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“…As shown in Figure 2C, four studies had a trend of elevated OR for the allele T (Albala et al, 2004;Takakura et al, 2005;Tavridou et al, 2009), and six studies showed a trend in the opposite direction (Lei et al, 1999;Ito et al, 1999;Carlsson et al, 2000;He, 2002;Duarte et al, 2003;Wang et al, 2011). No significant association was found between the FABP2 Ala54Thr polymorphism and obesity ( Figure 2C).…”

Section: A B Cmentioning

confidence: 99%

Association of the FABP2 Ala54Thr polymorphism with type 2 diabetes, obesity, and metabolic syndrome: a population-based case-control study and a systematic meta-analysis

Liu¹,

Wu²,

Han³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Previous studies have reported associations between the functional FABP2 Ala54Thr (rs1799883) polymorphism and type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome in different populations with conflicting results. We investigated the association between the FABP2 Ala54Thr polymorphism and T2DM (235 cases, 431 controls), obesity (377 cases, 431 controls), and metabolic syndrome (315 cases, 323 controls) by logistic regression analysis in a Chinese study cohort recruited from Yichang, Hubei Province. We then comprehensively reviewed the association of the FABP2 Ala54Thr polymorphism with T2DM, obesity, and metabolic syndrome via meta-analysis. The strength of association was assessed by odds ratios (ORs) with 95% confidence intervals (CIs). The FABP2 Ala54Thr polymorphism was significantly associated with obesity (AT vs AA:Y. Liu et al. 1156©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (1): 1155-1168 (2015) OR = 2.633, 95%CI = 1.065-6.663, P = 0.036; TT vs AA: OR = 4.160, 95%CI = 1.609-10.757, P = 0.003) and metabolic syndrome (TT vs AA: OR = 2.273, 95%CI = 1.242-4.156, P = 0.008) by logistic regression with adjustment for covariates. However, no significant association was found between T2DM and the FABP2 Ala54Thr polymorphism. We identified 24 studies on T2DM (4517 cases, 5224 controls), 9 studies on obesity (949 cases, 2002 controls), and 6 studies on metabolic syndrome (2194 cases, 3282 controls) by literature search. The metaanalyses revealed significant associations for metabolic syndrome (T allele: OR = 1.179, 95%CI = 1.015-1.362, P = 0.031) and T2DM (T allele: OR = 1.160, 95%CI = 1.08-1.24, P < 0.001), but no association for obesity (T allele: OR = 1.069, 95%CI = 0.925-1.235, P = 0.367).

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“…However, sib-pair analysis failed to detect any linkage of the FABP2 locus or the Ala54Thr polymorphism with diabetes-related phenotypes in other ethnic groups. The homozygous Thr54/Thr54 genotype has found the associations with higher fasting insulin levels and also TNF-α levels in 33 adult obese women (Albala et al, 2004). However, the findings of this study would need to be confirmed in studies involving a larger number of subjects.…”

Section: Impact Of Genetic Polymorphisms On Insulin Resistance 51mentioning

confidence: 44%

Impact of Genetic Polymorphisms on Insulin Resistance

Kömürcü-Bayrak¹

2012

Insulin Resistance

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Intestinal FABP2 A54T Polymorphism: Association with Insulin Resistance and Obesity in Women

Cited by 62 publications

References 40 publications

Influence of <i>ALA54THR</i> Polymorphism of Fatty Acid Binding Protein 2 on Lifestyle Modification Response in Obese Subjects

Influence of <i>ALA54THR</i> Polymorphism of Fatty Acid Binding Protein 2 on Lifestyle Modification Response in Obese Subjects

Association of the FABP2 Ala54Thr polymorphism with type 2 diabetes, obesity, and metabolic syndrome: a population-based case-control study and a systematic meta-analysis

Impact of Genetic Polymorphisms on Insulin Resistance

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