FABP2 Polymorphism Research Articles

Sex-specific association of FABP2 polymorphisms with the risk of obesity in the Tehran Cardio-Metabolic Genetic Study (TCGS)

FABP2 is one of the key genes involved in obesity development across different populations. However, there is no comprehensive report about the FABP2 contribution to obesity incidence among Iranians. Hence, the present study was designed to assess the probable role of FABP2 polymorphisms in obesity incidence in the Tehran Cardio- metabolic Genetic Study (TCGS) representative Iran population. Unrelated adults who had BMI information for at least 3 consecutive phases of the TCGS cohort were included. The control and case groups were defined as individuals who always had long-term persistent normal weight (20 < BMI < 25; n = 1526) and individuals who were long-term persistent obese (30 < BMI < 35; n = 1313), respectively. The logistic regression test was used to assess the possible association between SNPs located in and around the FABP2 gene with obesity. Also, we used Haploview and SHEsis to perform haplotype analysis to detect whether or not this chromosomal region is correlated with obesity. We found a gender-dependent association between the rs10857064 FABP2 and the risk of obesity. The presence of the rs10857064-G allele could significantly increase the risk of obesity only in women, not men (OR = 1.26; 95 % CI: 1.02–1.57; p = 0.03). Through haplotype analysis, we also detected that the TG haplotype containing rs7670862 and rs10857064 could significantly enhance the risk of obesity in women, further supporting the central role of rs10857064 in women’s long-term obesity risk. In the current study, we revealed that rs10857064-G FABP2 can significantly predispose women to develop obesity. It highlights the importance of different genetic variants in both genders, which could help us to distinguish more efficient obesity screening tests and treatments based on gender in the future.

Полиморфизм генов FTO (rs9939609), FABP2 (rs1799883) и PPARG (rs1801282) и риск ожирения у мужчин, проживающих в Кузбассе

Цель: изучение ассоциаций полиморфизма генов FTO, FABP2, PPARG и ожирения у жителей Кузбасса. Методы. Выборка для исследования составила 395 мужчин, жителей Кузбасса. Средний возраст испытуемых составил 59±7,7 года. Согласно анкетным данным, все обследованные мужчины отнесли себя к русской национальности. Частота ожирения в данной выборке (индекс массы тела&gt;30) составила 46,3%. Генотипирование полиморфных вариантов FTO (rs9939609), FABP2 (rs1799883) и PPARG (rs1801282) проводилось с использованием TaqMan PCR. Далее проводилась проверка ассоциации данных полиморфных вариантов с ожирением в различных моделях наследования. Результаты. Были выявлены ассоциации вариантов гена FTO rs9939609 с ожирением в кодоминантной (для генотипа T/A OR = 2,05; СI: 1,26-3,33; р = 0,004; для генотипа A/A (OR = 2,27; CI: 1,28-4,04; р= 0,004) и доминантной модели наследования (OR = 2,12; CI: 1,34-3,34 р= 0,001). Другие гены не показали значимой связи с ожирением в нашей выборке. Заключение. Вариант rs9939609 гена FTO ассоциирован с повышенным риском развития ожирения у мужчин, проживающих в Кузбассе. Purpose: To investigate the associations of FTO, FABP2, PPARG gene polymorphism and body mass index in Kuzbass residents. Methods. The sample for the study was 395 men, residents of Kuzbass. The average age of the subjects was 59±7.7 years. According to the questionnaire data, all the examined men referred themselves to the Russian nationality. The frequency of obesity in this sample (body mass index&gt;30) was 46.3%. Genotyping of 3 polymorphic variants: FTO (rs9939609), FABP2 (rs1799883), and PPARG (rs1801282) were performed using TaqMan PCR. The association of these polymorphic variants with obesity in various inheritance models was then tested. Results. The associations of FTO rs9939609 gene variants with obesity in the codominant (for genotype T/A OR = 2.05; CI: 1.26-3.33; p = 0.004; for genotype A/A (OR = 2.27; CI: 1.28-4.04; p = 0.004) and dominant inheritance models (OR = 2.12; CI: 1.34-3.34 p = 0.001) were detected. Other genes showed no significant association with obesity in our sample. Conclusion. The rs9939609 variant of the FTO gene is associated with an increased risk of obesity in Kuzbass residents.

The Influence of FTO, FABP2, LEP, LEPR, and MC4R Genes on Obesity Parameters in Physically Active Caucasian Men.

Obesity is a complex multifactorial abnormality that has a well-confirmed genetic basis. However, the problem still lies in identifying the polymorphisms linked to body mass and composition. Therefore, this study aimed to analyze associations between FTO (rs9939609), FABP2 (rs1799883), and LEP (rs2167270), LEPR (rs1137101), and MC4R (rs17782313) polymorphisms and obesity-related parameters. Unrelated Caucasian males (n = 165) were recruited. All participants had similar physical activity levels. The participants were divided into two groups depending on their body mass index (BMI) and fat mass index (FMI). All samples were genotyped using real-time polymerase chain reaction (real-time PCR). When tested individually, only one statistically significant result was found. The FTO A/T polymorphism was significantly associated with FMI (p = 0.01). The chance of having increased FMI was >2-fold higher for the FTO A allele carriers (p < 0.01). Gene–gene interaction analyses showed the additional influence of all investigated genes on BMI and FMI. In summary, it was demonstrated that harboring the FTO A allele might be a risk factor for elevated fat mass. Additionally, this study confirmed that all five polymorphisms are involved in the development of common obesity in the studied population and the genetic risk of obesity is linked to the accumulation of numerous variants.

Relationship between FABP2, PPARG, ADRB2 and ADRB3 gene polymorphisms predicting the risk of developing type 2 diabetes

Background and Aims: The study aimed to assess the possible association between different combinations of polymorphic variants of PPARG2(Pro12Ala), ADRB2 (Gln27Glu), ADRB2 (Agr16Gly), ADRB3 (Trp64Agr), and FABP2 (Thr54Ala) and risk of diabetes mellitus (DM).

Polymorphism in Apolipoprotein C3 (APOC3) and Fatty Acid-Binding Proteins (FABP2) Genes in Nondiabetic Dyslipidemic Patients: A Tertiary Care Hospital-Based Pilot Study

Context Dyslipidemia is a multifactorial disease in which lipoproteins play an important role as one of the early markers for coronary heart disease (CHD). Mixed dyslipidemia is common in people with diabetes mellitus, but nondiabetic dyslipidemics (NDD) remain unidentified for the risk of developing dyslipidemia and eventually CHD. Objectives This pilot study attempts to analyze the genetic basis of lipid metabolism alterations, emphasizing the association between fatty acid-binding protein-2 (FABP2-Ala54Thr) and apolipoprotein-C3 (APOC3-rs5128) genetic polymorphism, as a risk for developing dyslipidemia and CHD in NDD. Methods and Design Total 90 subjects—30 DD, 30 NDD, and 30 apparently healthy subjects representing Central India—were included. Biochemical analysis and DNA genotyping were done by polymerase chain reaction restriction fragment length polymorphism. Statistical Analysis The biochemical parameters were reported as means ± standard deviation. One-way analysis of variance test was used to compare biochemical parameters of three groups. Chi-squared test was done to compare genotype distributions. The strength of association was assessed by odds ratios (ORs) with 95% confidence intervals (CIs). All statistical analysis was done using SPSS-PC software and Graph Pad. Results In NDD, maximum polymorphism was observed followed by DD and least polymorphism was observed in controls. There was a significant association of APOC3 G allele with occurrence of hypertriglyceridemia ( p < 0.05); however, no such association was found for FABP2 A allele ( p > 0.05). Logistic regression analysis revealed APOC3 polymorphism to be significantly associated with dyslipidemia (OR = 2.6667, 95% CI = 1.0510–6.7663, p = 0.0341); no such association was found for FABP2 polymorphism (OR = 0.4643, 95% CI = 0.1641–1.3136, p = 0.1347). The triglyceride and cholesterol values in individuals with homozygous genotype indicate that genetic study is comparable to the biochemical findings in carriers of polymorphic allele than noncarriers, especially in NDD patients. Conclusions Pilot study indicates that the presence of APOC3 gene polymorphism is associated with pro-atherogenic dyslipidemia in nondiabetic patients and may raise risk of CHD. This information could be used for preventive strategies in NDD group that may otherwise go unnoticed.

FABP2, LEPR223, LEP656, and FTO Polymorphisms: Effect on Weight Loss 2 Years After Bariatric Surgery

Differences in weight loss outcomes after bariatric surgery may be related to individual preoperative characteristics. The aim of this study was to evaluate the potential effect of fatty acid binding protein-2 (rs1799883), leptin receptor (LEP223, rs1137101 and LEP656, rs1805094), and fat mass and obesity-related (rs9939609) genotypes on weight loss 2years after bariatric surgery in Brazilian patients. Prospective observational study involving 105 patients (lost to follow-up, 25.7%). In the preoperative period, patients were clinically evaluated and a fasting blood sample for genetic analysis (by real-time DNA amplification technique) was collected. From the patient's medical records, follow-up weight loss (3, 6, 12, 24months) was obtained. Percentage of excess weight loss (%EWL) was examined by pairwise comparison across the polymorphisms. At baseline, the mean weight was 127.5 (23.3) kg and age 43.1 (10.9) years old. The %EWL was significant over time (p < 0.01). Only the LEP223 genotype showed association (p < 0.01). Up to 6months after surgery, no differences were observed. At 12months, a significant difference (p = 0.03) between AA (n = 19) and GG (n = 34) groups was observed, with 76.5% EWL versus 52.0%, respectively. This difference remained at 24months. Other genotypes did not present any significant association. There is a different evolution of weight loss in carriers of the LEP223 after bariatric surgery. The AA genotype seems to be associated with a higher weight loss. However, this pattern was evident only at 12months after surgery.

Associations of the lipid genetic variants Thr54 ( FABP2) and -493T ( MTTP) with total cholesterol and low-density lipoprotein cholesterol levels in Mexican subjects.

ObjectiveMexico has one of the world’s highest rates of obesity, which is influenced by lipid-genetic and lifestyle factors. This study aimed to determine whether FABP2 (Ala54Thr) and MTTP (-493 G/T) genetic polymorphisms are associated with metabolic disorders in Mexican subjects.MethodsA total of 523 subjects participated in a cross-sectional study. Genotyping for FABP2 and MTTP was performed using real-time RT-PCR. Biochemical and anthropometric data were evaluated.ResultsThe genetically at-risk group (Thr54/-493T) was associated with significantly higher total and low-density lipoprotein cholesterol levels (difference between genetically at-risk group and wild-type group: 10.6 mg/dL and 8.94 mg/dL, respectively). Carriers within the genetically at-risk group had a significantly higher prevalence rate of hypercholesterolaemia (42.5% vs. 32.0%) and higher LDL-C levels (37.6% vs. 26.4%) than did non-carriers.ConclusionsSubjects who are genetically at risk (Thr54/-493T) have higher total cholesterol levels, low-density lipoprotein cholesterol levels, and prevalence rate of hypercholesterolaemia. These findings highlight the importance of basing nutritional intervention strategies for preventing and treating chronic diseases on individual genetic characteristics.

Association between ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133), FTO (rs9939609) Genes Polymorphism and Type 2 Diabetes with Dyslipidemia.

Diabetic dyslipidemia is one of the leading causes of coronary artery disease (CAD) death. Genetic and environmental factors play an important role in the development of type 2 diabetes mellitus (T2DM) and dyslipidemia. The present study was aimed to investigate the association of ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133) and FTO (rs9939609) genes polymorphism in T2DM with dyslipidemia. Totally, 559 subjects including 221 T2DM cases with dyslipidemia, 158 T2DM without dyslipidemia and 180 controls were enrolled. ACE genes polymorphism was evaluated by polymerase chain reaction (PCR), while MTHFR, FABP2, FTO genes polymorphisms were evaluated by PCR and restriction fragment length polymorphism (RFLP). Significant association of ACE and MTHFR genes polymorphisms were found in both group of cases [T2DM with dyslipidemia (P<0.001, and P=0.008, respectively) and T2DM without dyslipidemia (P=0.003, and P=0.010, respectively)] while FABP2 and FTO genes polymorphisms were significantly associated with T2DM without dyslipidemia (P=0.038, and P= 0.019, respectively). This study concludes that ACE, FABP2, FTO and MTHFR genes are associated with T2DM. Additionally, it also seems that ACE and MTHFR genes might be further associated with the development of dyslipidemia in T2DM cases.

OS 08-01 ASSOCIATION OF ACE, FABP2, PPARG2, GST, FTO AND CYP46A1 GENES POLYMORPHISM WITH ESSENTIAL HYPERTENSION AMONG NORTH INDIAN POPULATION

Objective: Hypertension (HTN) is the most common cardiovascular disease and is assuming epidemic proportions in developing countries. Genetic and environmental factors play important role in the development of hypertension.The objective of this study was to investigate the possible association of ACE, FABP2, PPARG2, GST, FTO and CYP46A1 genes polymorphism and susceptibility of individuals to HTN. Design and Method: This case control study includes 123 essential HTN cases and 102 controls. ACE, GST genes polymorphisms were evaluated by PCR and FABP2, PPARG2, FTO, CYP46A1 genes polymorphisms were evaluated by PCR-RFLP methods. Results: The mean age of cases and controls were 41.32 ± 11.39 years and 40.13 ± 10.28 years. Frequencies of ACE II, ID, DD genotypes in essential HTN cases and controls were 22.76%, 63.42%, 13.82% and 11.77%, 60.78%, 27.45%; respectively. Frequencies of FABP2 AA, AT, TT in cases and controls were 11.38%, 70.74%, 17.88% and 20.59%, 64.71%, 14.70%. Frequencies of PPARG2 CC, CG, GG genotype in cases and control were 27.65%, 65.85%, 6.50% and 21.57%, 37.26%, 41.17%. Frequency of GSTM1 null, GSTT1 null genotypes in cases and controls were 41.47%, 5.69% and 52.95%, 4%; respectively. Frequencies of FTO AA, AT, TT genotype in cases and control were 1.63%, 68.29%, 30.08% and NA, 75.49%, 24.51%. Frequencies of CYP46A1 CC, CT, TT genotype in cases and control were 17.08%, 33.33%, 49.59% and 3.93%, 28.43%, 67.64%. Significant differences were obtained in the frequencies of ACE II genotype (p = 0.032), PPARG2 CG, GG genotype (p < 0.001) CYP46A1 CC, TT genotype (p = 0.002, 0.006). Conclusions: Findings of this study suggest that ACE, PPARG2, CYP46A1 genes were significantly associated with essential HTN cases in North Indian populations.

The Ala54Thr Polymorphism of the Fatty Acid Binding Protein 2 Gene Modulates HDL Cholesterol in Mexican-Americans with Type 2 Diabetes.

The alanine to threonine amino acid substitution at codon 54 (Ala54Thr) of the intestinal fatty acid binding protein (FABP2) has been associated with elevated levels of insulin and blood glucose as well as with dyslipidemia. The aim of this study was to characterize the effect of this FABP2 polymorphism in Mexican-Americans with type 2 diabetes (T2D) in the context of a three-month intervention to determine if the polymorphism differentially modulates selected clinical outcomes. For this study, we genotyped 43 participant samples and performed post-hoc outcome analysis of the profile changes in fasting blood glucose, HbA1c, insulin, lipid panel and body composition, stratified by the Ala54Thr polymorphism. Our results show that the Thr54 allele carriers (those who were heterozygous or homozygous for the threonine-encoding allele) had lower HDL cholesterol and higher triglyceride levels at baseline compared to the Ala54 homozygotes (those who were homozygous for the alanine-encoding allele). Both groups made clinically important improvements in lipid profiles and glycemic control as a response to the intervention. Whereas the Ala54 homozygotes decreased HDL cholesterol in the context of an overall total cholesterol decrease, Thr54 allele carriers increased HDL cholesterol as part of an overall total cholesterol decrease. We conclude that the Ala54Thr polymorphism of FABP2 modulates HDL cholesterol in Mexican-Americans with T2D and that Thr54 allele carriers may be responsive in interventions that include dietary changes.

Influence of ApoE and FABP2 polymorphisms and environmental factors in the susceptibility to gallstone disease

Background. Gallstone disease (GSD) is a common chronic disease in the Western hemisphere, yet environmental and genetic factors may be responsible for the variations in the prevalence of GSD among populations.Aim. To analyze the relationship of the ApoE and FABP2 polymorphisms with diet, physical activity and emotional health in patients with GSD from West Mexico.Material and methods. A total of 120 patients with GSD and 370 healthy subjects were enrolled. Anthropometric, biochemical, nutritional, clinical and physical activity parameters were measured. ApoE and FABP2 genotypes were assesed by PCR-RFLPs assays.Results: ApoE E3/E4 genotype and the ApoE E4 allele was highly prevalent among the GSD patients compared to the controls (32% vs. 12.0% and 22% vs. 8.4% respectively p < 0.01). Patients with the Apo E4 allele showed an upward trend of cholesterol levels compared to non-Apo E4 allele carriers (E4 186 ± 30 mg/dL; E3 143 ± 37 mg/dL; E2 129 ± 34 mg/dL). High triglyceride levels were associated with patients that were FABP2 Thr54 allele carriers (p < 0.05) but lacked association with GSD. This may be due to changes in dietary fats after GSD diagnosis, masking the clinical course of the disease. Sedentary lifestyle and negative emotions were detected in 83% and 63% of patients, respectively.Conclusion. These data suggest that the Apo E4 allele could confer genetic susceptibility for the development of GSD among the Mexican population. The Ala54Thr polymorphism of FABP2 was associated with high triglycerides levels, but not to GSD; suggesting that environmental factors modulate such susceptibility.

Association of ACE, FABP2 and GST genes polymorphism with essential hypertension risk among a North Indian population

Background: Hypertension has a multi-factorial background based on genetic and environmental interactive factors. ACE, FABP2 and GST genes have been suggested to be involved in the development of hypertension. However, the results have been inconsistent.Aim: The present study was carried out to investigate the association of ACE (rs4646994), FABP2 (rs1799883) and GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphism with essential HTN cases and controls.Subjects and methods: This study includes 138 essential hypertension (HTN) patients and 116 age-, sex- and ethnicity-matched control subjects. GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphisms were evaluated by multiplex PCR, ACE (rs4646994) gene polymorphisms by PCR and FABP2 (rs1799883) gene polymorphisms by PCR-RFLP method.Results: Significant differences were obtained in the frequencies of ACE DD, II genotype (p = 0.006, 0.003), GSTT1 null, GSTM1 positive genotype (p = 0.048, 0.010) and FABP2 Ala54/Ala54 genotype (p = 0.049) between essential HTN cases and controls.Conclusion: It is concluded that ACE (rs 4646994), FABP2 (rs1799883) and GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphism are associated with HTN. Further investigation with a larger sample size may be required to validate this study.

Fatty acid-binding protein 2 Ala54Thr polymorphism among psoriatic patients in Çanakkale, Turkey

A single nucleotide polymorphism (G-to-A) in codon 54 of exon two resulting in an alanine to threonine substitution and we hypothesized that, in psoriatic patients Ala54Thr carriers would have increased risk for psoriasis than Ala54-homozygous counterparts. 141 psoriatic patients and 131 healthy individuals who gave informed consent, were enrolled to study. FABP2 polymorphism was evaluated with melting curve analysis (RealTime PCR). Genotype frequencies were estimated by gene counting. In consistency of genotype frequencies with the Hardy-Weinberg equilibrium was tested using a Chi- Square. Odds ratio (OR) and 95% confidence interval were calculated to estimate the risks related to (FABP2) Ala54Thr polymorphism. To calculate the significance of OR, Fisher’s exact test was used. Eighteen patients (12.8%) had Ala54/Ala54 (wild group) and 118 (83.7%) patients a mutant genotype, Ala54/Thr54 (55 patients, 39%) or Thr54/Thr54 (63 patients, 44.7%). In control group, ten subjects (7.6%) had the genotype Ala54/Ala54 (wild-type group) and 121 (92.4%) participants had the genotype Ala54/Thr54 (n=47, 35.9%) or Thr54/Thr54 (n=74, 56.5%). The genotype distribution were consistent with Hardy-Weinberg equilibrium for psoriatic and healthy groups (χ²calculated: 0.07 2 nd degree).When psoriatic patients with homozygote “AA” or heterozygote genotype “GA” were compared with the ones with normal genotype, no statistical correlation was found (ORAAvs GG:0.47; 95%CI: 0.20-1.09; p:0.08 and ORGA vs GG:0.65; 95%CI: 0.27-1.55; p:0.33). Asidethe transition of G to A at codon 54 of FABP2 were not increased psoriasis risk in statistically significant manner (OR: 0.68;95% CI: 0.47-0.99; p: 0.046). The overall odds ratio was found 0.697 (p=0.055) by Armitage’s Trend Test. We found no correlation between allelic distribution or genotype frequency of FABP2 Ala54Thr polymorphism and psoriasis. In conclusion, our present results suggest that FABP2 genotypes were not statistically significant and unsuitable to use as dependent determinants of the risk. The alanine to threonine substitution of FABP2 gene can’t be used as diagnostic marker for psoriasis and validation of these findings require to replicate within largescale study group to find real association.

Polymorphism of FABP2 and PPARG2 genes in risk prediction of cataract among North Indian population

BackgroundCataract is the leading cause of bilateral blindness in India. It has been reported that cataract is responsible for 50–80% of the bilaterally blind in the country. Cataract formation is a natural part of the ageing process. At present, adequate data are not available regarding the FABP2 and PPARG2 gene polymorphisms and their susceptibility with cataract cases in the North Indian population. Thus, the present study was carried out to investigate the association of FABP2 and PPARG2 gene polymorphisms with cataract cases and controls. Materials and methodsThis study includes 130 cataract cases and 118 controls. FABP2 and PPARG2 gene polymorphisms in cases and controls were evaluated by PCR-RFLP. ResultsFrequencies of Ala54Ala, Ala54Thr and Thr54Thr genotypes in FABP2 gene in cataract cases and controls were 50.76%, 39.23%, 10% and 25.42%, 61.86%, 12.71% respectively. The PPARG2 gene CC, CG, GG genotype frequencies were 11.53%, 87.69% and 0.76% in cases and 21.18%, 39.83% and 38.98% in healthy controls respectively. Significant differences were observed in the frequencies of FABP2 Ala54Ala, Ala54Thr genotype (p<0.05) and PPARG2 CC, CG, GG genotype (p<0.05) between cases and controls. ConclusionThe findings of this study suggest that FABP2 and PPARG2 gene polymorphisms can be an informative marker for early identification of population at risk of cataract. The potential role of FABP2 and PPARG2 gene polymorphisms as a marker of susceptibility to cataract needs further studies in a larger number of patients.

Genotype and allele frequencies of the intestinal fatty acid binding protein-2 gene in two Arab populations

Objective: Intestinal fatty acid binding protein (IFAPB) participates in the uptake, intracellular metabolism and/or transport of long chain fatty acids. A polymorphism at codon 54 in exon 2 of FABP2 gene, which encodes for the IFAPB, exchanges an Alanine for Threonine. FABP2 gene polymorphism could modify the uptake of fatty acids, and it could correlate with risk of several diseases. In the light of the potential role of the FABP2 polymorphism, the aim of this study was to determine the frequency of the Ala54Thr FABP2 polymorphism in two Middle Eastern Arab Populations. Materials and Methods: Genotyping was investigated in 182 and 120 unrelated healthy subjects from Bahrain and Jordan, respectively. A PCR-RFLP assay was applied for determination of Ala54Thr (rs1799883) FABP2 polymorphism. Allele frequencies were calculated by direct counting. Hardy Weinberg Equilibrium was evaluated using a Chi- square goodness of fit test. Results: In the studied Bahraini subjects, 52.8% were homozygous for the Ala54/Ala54 genotype, 35.7% were heterozygous for the Ala54/Thr54 genotype and 11.5% were homozygous for the Thr54/Thr54 genotype. The gene frequencies obtained in Jordanians were: 48.3%, 43.3% and 8.4% for Ala54/Ala54; Ala54/Thr54 and Thr54/Thr54 genotypes, respectively. The frequencies of the allele Ala54 and the allele Thr54 of the FABP2 gene were found to be 0.706 and 0.294 for Bahrainis and 0.700 and 0.300 for Jordanians. These results revealed a similar population polymorphism frequency as in previous European and Arab populations' studies. Conclusion: This is the first study to investigate the population frequency of the Thr54 allele in Bahraini and Jordanian populations.

Association of angiotensin-converting enzyme (ACE) and fatty acid binding protein 2 (FABP2) genes polymorphism with type 2 diabetes mellitus in Northern India

Type 2 diabetes mellitus (T2DM) is growing in an epidemic manner across the world with an expected doubling of the incidence to millions of affected individuals in the last decades. At present, adequate data are not available regarding the ACE and FABP2 polymorphisms and their susceptibility with T2DM cases in the North Indian population. Thus we conceived the need for further study of ACE (I/D) and FABP2 (Ala54Thr) genes polymorphism and its susceptibility to T2DM in the North Indian population. In this study, a total of 300 subjects (including 190 T2DM cases and 110 controls) participated. ACE and FABP2 gene polymorphisms in the cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism. The frequencies of ACE I/I, I/D and D/D genotypes in T2DM cases and controls were 28.73%, 55.17%, 16.09% and 13.63%, 57.95%, 28.40%, respectively. The frequencies of FABP2 Ala54Ala, Ala54Thr and Thr54Thr in T2DM cases were 18.39%, 66.66%, 14.94% and 22.72%, 61.36%, 15.90% in controls, respectively. ACE I/I genotype was significantly more frequent in cases as compared to controls (p = 0.003, χ(2) = 9.13). It appears that the ACE I/I genotype frequency was significantly higher in the T2DM cases as compared to the controls.

APOE and FABP2 Polymorphisms and History of Myocardial Infarction, Stroke, Diabetes, and Gallbladder Disease

Dysfunctional lipid metabolism plays a central role in pathogenesis of major chronic diseases, and genetic factors are important determinants of individual lipid profiles. We analyzed the associations of two well-established functional polymorphisms (FABP2 A54T and APOE isoforms) with past and family histories of 1492 population samples. FABP2-T54 allele was associated with an increased risk of past history of myocardial infarction (odds ratio (OR) = 1.51). Likewise, the subjects with APOE4, compared with E2 and E3, had a significantly increased risk of past history myocardial infarction (OR = 1.89). The OR associated with APOE4 was specifically increased in women for past history of myocardial infarction but decreased for gallstone disease. Interactions between gender and APOE isoforms were also significant or marginally significant for these two conditions. FABP2-T54 allele may be a potential genetic marker for myocardial infarction, and APOE4 may exert sex-dependent effects on myocardial infarction and gallbladder disease.

Polymorphisms in fatty acid binding protein 5 show association with type 2 diabetes

Genes for the fatty acid binding proteins (FABP) family encode small 14–15kDa cytosolic proteins and can be regulated during type 2 diabetes mellitus (T2DM) and obesity. This study compared association of single nucleotide polymorphisms (SNPs) in FABP1-5 with T2DM in different ethnic groups. Associations with T2DM of SNPs in these proteins were assessed in African American (AA), non-Hispanic White (NHW), and Hispanic American (HA) individuals. A total of 650 DNA samples were genotyped; control samples were obtained from Coriell's North American Human Variation Panel Repository (NAHVP) of apparently healthy individuals and T2DM cases were taken from the American Diabetes Association GENNID Study. The rs454550 SNP of FABP5 showed a significant association with T2DM in NHW (OR: 9.03, 95% CI: 1.13–71.73, p=0.014). Our analysis also identified a new FABP5 SNP (nSNP) that showed a significant association with T2DM in NHW (OR: 0.44, 95% CI: 0.19–0.99, p=0.045) and AA (OR: 0.17, 95% CI: 0.03–0.80, p=0.016). The Ala54Thr FABP2 polymorphism was significantly associated with T2DM in HA individuals only (OR: 1.85, 95% CI: 1.05–3.27, p=0.032). All other FABP SNPs did not show association with T2DM. These findings suggest a potential distinct role(s) of SNPs in FABP5 and FABP2 genes in T2DM in different populations.

Polymorphism of the FABP2 gene: a population frequency analysis and an association study with cardiovascular risk markers in Argentina

BackgroundThe FABP2 gene encodes for the intestinal FABP (IFABP) protein, which is expressed only in intestinal enterocytes. A polymorphism at codon 54 in exon 2 of the FABP2 gene exchanges an Alanine (Ala), in the small helical region of the protein, for Threonine (Thr). Given the potential physiological role of the Ala54Thr FABP2 polymorphism, we assess in this study the local population frequency and analyze possible associations with five selected markers, i.e. glycemia, total cholesterol, body mass index (BMI), hypertension, and high Cardiovascular Risk Index (CVR index).MethodsWe studied 86 men and 116 women. DNA was extracted from a blood drop for genotype analysis. Allele frequencies were calculated by direct counting. Hardy Weinberg Equilibrium was evaluated using a Chi-square goodness of fit test.For the polymorphism association analysis, five markers were selected, i.e. blood pressure, Framingham Risk Index, total cholesterol, BMI, and glycemia.For each marker, the Odds Ratio (OR) was calculated by an online statistic tool.ResultsOur results reveal a similar population polymorphism frequency as in previous European studies, with q = 0.277 (95% confidence limits 0.234–0.323). No significant association was found with any of the tested markers in the context of our Argentine nutritional and cultural habits. We did, however, observe a tendency for increased Cholesterol and high BMI in Thr54 carriers.ConclusionThis is the first study to look at the population frequency of the Thr54 allele in Argentina. The obtained result does not differ from previously reported frequencies in European populations. Moreover, we found no association between the Thr54 allele and any of the five selected markers. The observed tendency to increased total cholesterol and elevated BMI in Thr54 carriers, even though not significant for p < 0.1 could be worth of further investigation to establish whether the Thr54 variant should be taken into consideration in cardiovascular prevention strategies.

Codon 54 polymorphism of the fatty acid binding protein (FABP) 2 gene is associated with increased cardiovascular risk in the dyslipidemic diabetic participants of the veterans affairs HDL intervention trial (VA-HIT)

The threonine (Thr) for alanine (Ala) codon 54 polymorphism of the fatty acid binding protein (FABP) 2 gene, when compared to the wild type, is associated with dyslipidemia. Since dyslipidemia is common in diabetes and is associated with increased cardiovascular risk, we tested the hypothesis that Thr-54 is associated with increased cardiovascular risk in patients with diabetes. The secondary prevention veterans affairs HDL intervention trial (VA-HIT) was carried out in patients with dyslipidemia. The DNA of trial participants ( n = 776) was screened for the Thr-54 polymorphism and cardiovascular endpoints were monitored. The polymorphism was detected in 370 (47.7%). For first occurrence of the primary endpoint [myocardial infarction (MI) or coronary heart disease (CHD) death] the hazard ratio (HR) and confidence intervals (Cox proportional hazards model) was 2.5 (1.2, 5.3) p = .02 in diabetic carriers of Thr-54 versus carriers without diabetes or fasting glucose >7 mmol/L. For the expanded endpoint (stroke, MI or CHD death), the corresponding HR was 3.0 (1.4, 5.4) p = .0003 and for the stroke alone the corresponding HR was 3.5 (1.4–8.9) p = .01. The higher cumulative incidence of the expanded endpoint in diabetic participants carrying the FABP2 polymorphism versus non-diabetic carriers was consistently present throughout the 5 years of the study ( p = .0002). We conclude that based on the VA-HIT data, the Thr-54 polymorphism of the FABP2 gene is associated with a 2–3.5-fold increase in cardiovascular risk in dyslipidemic men with diabetes compared to their non-diabetic counterparts.