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1.
T Hayakawa Y Nagai E Nohara H Yamashita T Takamura T Abe G Nomura K Kobayashi 《Metabolism: clinical and experimental》1999,48(5):655-657
An alanine to threonine substitution at codon 54 of the fatty acid binding protein 2 (FABP2) gene has been associated with insulin resistance in Pima Indians and with obesity in aboriginal Canadians. We investigated whether this polymorphism contributes to obesity and insulin resistance in 258 Japanese subjects. Thirty-six subjects (13.9%) were homozygous for the Thr54 allele, 106 (41.1%) were heterozygous for the Ala54/Thr54 allele, and 116 (45.0%) were homozygous for the Ala54 allele. The frequency of the Thr54 allele was 0.34 and did not differ significantly between men and women. The incidence of non-insulin-dependent diabetes mellitus (NIDDM) was not different among the three genotypes. The variation at codon 54 of the FABP2 gene was not associated with obesity, hypertension, dyslipidemia, hyperuricemia, or hyperinsulinemia. These results suggest that the polymorphism at codon 54 of the FABP2 gene is not a major contributing factor to obesity and insulin resistance in Japanese subjects. 相似文献
2.
K. Yamada X. Yuan S. Ishiyama K. Koyama F. Ichikawa A. Koyanagi W. Koyama K. Nonaka 《Diabetologia》1997,40(6):706-710
Summary Alanine to threonine substitution at codon 54 of the fatty acid-binding protein 2 (FABP2) gene was recently shown to be associated
with insulin resistance in Pima Indians. It has been hypothesized that the mutation may result in enhanced intestinal uptake
of fatty acids, and thereby an impairment of insulin action. We analysed the association of the Ala54Thr substitution with
insulin sensitivity and abdominal fat thickness in 395 Japanese men aged 50.5 ± 8.8 years (mean ± SD) with a body mass index
of 24.4 ± 3.0 kg/m2. The frequency of the Thr54 allele was 0.34. Although the polymorphism was not significantly associated with diabetes or
impaired glucose tolerance, subjects homozygous for the Thr54 allele had higher basal insulin levels. Analysis by homeostasis
model assessment showed an association between the amino acid substitution and greater insulin resistance, and slightly higher
beta-cell function. Oral glucose tolerance tests performed in 392 subjects without fasting hyperglycaemia showed higher 2-h
insulin concentrations in individuals homozygous for the Thr54 allele when compared with heterozygotes or homozygotes for
the Ala54 allele. No significant association was obtained between the polymorphism of the FABP2 gene and body mass index.
However, ultrasound measurements of abdominal fat thickness revealed a greater accumulation of intra-abdominal fat in subjects
homozygous for the Thr54 allele, whereas subcutaneous fat thickness was not associated with the polymorphism. These observations
suggest that the Ala54Thr substitution in the FABP2 gene is associated with insulin resistance in Japanese men, and that visceral
fat accumulation might be involved in the impaired insulin action associated with the substitution. [Diabetologia (1997) 40:
706–710]
Received: 30 December 1996 and in revised form: 10 March 1997 相似文献
3.
Kim CH Yun SK Byun DW Yoo MH Lee KU Suh KI 《Metabolism: clinical and experimental》2001,50(4):473-476
The alanine to threonine substitution at codon 54 (Ala54Thr) of the fatty acid binding protein 2 (FABP2) gene has been reported to be associated with increased fat oxidation and insulin resistance in several populations. It has been hypothesized that Ala54Thr substitution results in enhanced intestinal uptake of fatty acids and thereby an impairment of insulin action, but this hypothesis has not been proven in vivo. We studied the association between the Ala54Thr polymorphism of the FABP2 gene and intestinal (3)H-oleic acid absorption, as well as basal insulin level, basal metabolic rate, and fat oxidation rate in 96 healthy young Korean men. Among our subjects, the allele frequency of the Ala54Thr substitution was 0.34. Subjects with Thr54-encoding allele were found to have a higher mean fasting plasma insulin concentration and a higher basal fat oxidation rate compared with the subjects who were homozygous for the Ala54-encoding allele. However, there was no significant difference in basal metabolic rate or (3)H-oleic acid absorption according to the FABP2 gene polymorphism. These results suggest that the Ala54Thr substitution in the FABP2 gene is associated with increased fat oxidation and hyperinsulinemia in normal Korean men, but these effects are not mediated by an increase in the intestinal fatty acid absorption. 相似文献
4.
Takakura Y Yoshioka K Umekawa T Kogure A Toda H Yoshikawa T Yoshida T 《Diabetes research and clinical practice》2005,67(1):36-42
We investigated the relationship between Ala54Thr variant allele of the fatty acid-binding protein 2 (FABP2) gene (Ala54Thr) and development of obesity in Japanese obese women. FABP2 genotypes were determined with a fluorescent allele-specific DNA primer assay system. Body weight, waist and hip circumference, amounts of visceral and subcutaneous white adipose tissue measured by computed tomography (CT) were compared between subjects with Thr allele and without Thr allele before and after the diet and exercise therapy in 80 Japanese obese women. The frequency of the Thr54 allele did not differ between obese and control subjects (0.388 versus 0.329, respectively). In subjects with Ala/Thr and Thr/Thr genotype, adjusted resting metabolic rate (RMR) was significantly lower than the subjects with Ala/Ala genotype. Subjects with the Thr54 allele showed significantly greater waist circumference after diet and exercise therapy than subjects with Ala/Ala genotype. They also demonstrated greater body weight at 20 years of age compared to subjects with Ala/Ala genotype. In conclusion, Thr54 allele of FABP2 has associations with lower adjusted resting metabolic rate, resistance in reducing visceral white adipose tissue (WAT) and early onset of obesity in Japanese obese women. 相似文献
5.
Codon 54 polymorphism of the fatty acid binding protein gene and insulin resistance in the Japanese population. 总被引:4,自引:0,他引:4
K Ito K Nakatani M Fujii A Katsuki K Tsuchihashi K Murata H Goto Y Yano E C Gabazza Y Sumida Y Adachi 《Diabetic medicine》1999,16(2):119-124
AIM: To determine the relationship of the polymorphism at codon 54 of the intestinal fatty acid binding protein gene (FABP2) with insulin resistance and susceptibility to Type 2 diabetes mellitus (DM) in the Japanese population. METHODS: We evaluated the polymorphism by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 150 Type 2 DM patients and 147 healthy control subjects. The frequency of alleles encoding threonine (Thr54) and alanine (Ala54) at codon 54 of FABP2 in Type 2 DM patients was compared with that of healthy controls. Insulin sensitivity was assessed by the hyperinsulinaemic euglycaemic clamp in Type 2 DM patients with Ala54 homozygotes, Ala54/Thr54 heterozygotes and Thr54 homozygotes and by homeostasis model assessment (HOMA) in the nondiabetic group. RESULTS: The frequency of alleles encoding Ala54 and Thr54 was 0.59 and 0.41 in Type 2 DM patients, respectively, similar to that observed in nondiabetic controls (0.64 for Ala54 and 0.36 for Thr54). Insulin sensitivity was not significantly different between subjects with and without Thr54 allele either within the DM group or healthy controls. CONCLUSIONS: The allele encoding threonine in the FABP2 does not predispose to Type 2 DM or insulin resistance in the Japanese population. 相似文献
6.
Okada T Sato NF Kuromori Y Miyashita M Iwata F Hara M Harada K Hattori H 《Journal of atherosclerosis and thrombosis》2006,13(4):192-196
BACKGROUND: Alanine-for-threonine substitution at codon 54 (A54T polymorphism) in the fatty acid-binding protein 2 gene (FABP2) has been associated with hypertriglyceridemia and insulin resistance. Impairment in the activity of delta 6 and 5 desaturases is also supposed to be a factor predisposing the development of insulin resistance syndrome. AIM: We investigated the relationship between A54T polymorphism in FABP2 and the impairment of long-chain polyunsaturated fatty acid metabolism in obese children. METHODS: Thirty-two obese children participated. During the study, the children continued their habitual diet, which was documented in a 3-day food record using household measures. Anthropometry was performed, and serum lipid and fatty acid composition in plasma were analyzed. The polymorphism of codon 54 in the FABP 2 gene was analyzed. RESULTS: The allele frequency was 0.66 and 0.34 for Ala54 and Thr54, respectively. There were no significant differences in age, body mass index, fasting serum glucose, insulin or serum lipoproteins among the three polymorphism groups. These were also no significant differences in the intake of energy, the percentage of energy nutrients or in the dietary lipid composition. The content of arachidonic acid (AA) in plasma was lowest in Thr/Thr54 (p < 0.05). The indices of delta-6 desaturase (D6D) activity in Thr/Thr54 were significantly lower than in Thr/Ala54 or Ala/Ala54 (p < 0.05, p < 0.01, respectively). CONCLUSIONS: In obese children, Thr/Thr54 of the FABP 2 gene is associated with impaired activation of D6D and reduced AA content. The results in the LCPUFA profile suggest that Thr/Thr54 may predispose the to development of insulin resistance. 相似文献
7.
Alanna M. Chamberlain Pamela J. Schreiner Myriam Fornage Catherine M. Loria David Siscovick Eric Boerwinkle 《Metabolism: clinical and experimental》2009,58(9):1222-1228
The Thr54 allele of the intestinal fatty acid–binding protein Ala54Thr functional polymorphism (FABP2) is associated with increased fat oxidation and insulin resistance. We determined the cross-sectional associations of the FABP2 gene with lipid levels and insulin resistance in 2148 participants who completed the year-20 examination of the Coronary Artery Risk Development in Young Adults (CARDIA) study. No significant difference in total cholesterol, low-density or high-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol to total cholesterol ratio, or homeostasis model assessment of insulin resistance (HOMA-IR) was found between FABP2 genotypes. However, in the presence of a high–saturated fat diet (≥53.2 g/d, the 90th percentile for the population), the AA/AG genotypes (carriers of the Thr54 allele) of FABP2 had statistically significantly higher levels of log(HOMA-IR) (P = .006) and a lower high-density lipoprotein cholesterol to total cholesterol ratio (P = .03), and borderline statistically significantly higher levels of total cholesterol, low-density lipoprotein cholesterol, and log(triglycerides) (P values = .08, .07, and .05, respectively) compared with those with the GG genotype (Ala54 homozygotes). Lipid levels and log(HOMA-IR) did not vary by genotype with saturated fat intake less than 53.2 g/d. Limiting dietary saturated fat intake may be particularly important among carriers of the A allele of FABP2. 相似文献
8.
Erkkilä AT Lindi V Lehto S Pyörälä K Laakso M Uusitupa MI 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2002,12(2):53-59
BACKGROUND AND AIM: It has been suggested that the threonine (Thr) 54 allele of the intestinal fatty acid binding protein 2 (FABP2) gene is associated with insulin resistance and affects the fatty acid composition of serum lipids. Our aim was to investigate the frequency of the alanine (Ala) 54Thr polymorphism of the FABP2 gene in patients with coronary heart disease (CHD), and the association between the polymorphism and the markers of metabolic syndrome, serum lipid levels and the fatty acid profile of serum lipids. METHODS AND RESULTS: A total of 414 CHD patients (mean age 61 years, range 33-74) participated in the cross-sectional EUROASPIRE (European Action on Secondary Prevention through Intervention to Reduce Events) Study. Markers of metabolic syndrome included fasting plasma glucose concentration, serum high-density lipoprotein cholesterol and triglycerides (TG), waist circumference, the waist/hip ratio, body mass index (BMI) and blood pressure (BP). The frequency of the Thr54 allele was similar in the CHD patients (27.2%) and control subjects from two independent studies (27.8% and 28.7%). There were no significant differences in plasma glucose, serum lipids, BP, BMI, waist circumference or waist/hip ratio among the genotypes. Genotype frequency was not associated with the prevalence of diabetes or metabolic syndrome, but metabolic syndrome (as defined by National Cholesterol Education Program criteria) tended to be more frequent in subjects with the Thr/Thr genotype (p = 0.095). There were no differences in the fatty acid profiles of serum cholesteryl esters, TG or phospholipids among the genotypes. CONCLUSIONS: The Ala54Thr polymorphism of the FABP2 gene is not associated with CHD, markers of the metabolic syndrome, or the fatty acid profile of serum lipids in Finnish CHD patients. 相似文献
9.
Aims/hypothesis An Ala54Thr polymorphism in the FABP2 gene has previously been associated with insulin resistance and lipid oxidation rates in Pima Indians. Ala54Thr functionally alters the proteins ability to bind and transport dietary fatty acids. In the current report, we sought additional functional variation in FABP2 by sequencing putative regulatory regions.Methods More than 1.2 Kb of the putative promoter of FABP2 was sequenced in 20 Pima subjects. Variations were genotyped in 84 additional Pima Indian subjects to assess haplotype combinations. Functional activities of variant and nonvariant promoters were compared in Caco-2 cells transfected with luciferase reporter constructs.Results Seven variations were identified in the FABP2 promoter in Pima Indians. Genotypes of these variants were in complete concordance with each other, and were in complete concordance with Ala54Thr. Therefore, only two promoter alleles were observed in Pima Indians, an Ala54-associated promoter and a Thr54-associated promoter. In contrast, genotyping of these variants in Caucasian DNA showed multiple genotypic combinations. In vitro reporter assays indicated that the Thr54-associated promoter in Pima Indians resulted in a threefold reduction in promoter activity as compared to Ala54-associated promoter.Conclusion/interpretation Two functional variations exist in FABP2—the coding Ala54Thr and the variant promoter. In the Pima Indian population, but not the Caucasian population, these two functional variants are always carried on the same allele. Therefore, some of the in vivo phenotypic associations previously attributed to the Ala54Thr substitution, which alters binding characteristics of the protein, could instead be due to promoter variation, which alters expression levels.Abbreviations A,
Adenosine
- Ala,
alanine
- CEPH,
genomic DNA set, originating from Caucasians from Utah, USA
-
FABP2,
intestinal fatty acid binding protein gene
- G,
guanosine
- IFABP,
intestinal fatty acid binding protein
- PCR,
polymerase chain reaction
- Thr,
threonine 相似文献
10.
Daniel Antonio de Luis Manuel Gonzalez Sagrado Rocio Aller Olatz Izaola Rosa Conde 《Metabolism: clinical and experimental》2011,60(5):664-668
The prevalence of metabolic syndrome (MS) has been estimated to be approximately 25% of the population at large. A transition G to A at codon 54 of fatty acid-binding protein 2 (FABP2) results in an amino acid substitution (ala54 to Thr54), and this polymorphism was associated with some cardiovascular risk factors. The aim of our study was to investigate the relationship between MS and Thr54 polymorphism in the FABP2 gene in obese patients. A population of 750 (body mass index >30) obese patients was analyzed in cross-sectional survey. Bioimpedance, blood pressure, and serial assessment of nutritional intake with 3-day written food records and biochemical analysis were performed. The statistical analysis was performed for the combined Ala54/Thr54 and Thr54/Thr54 as a mutant group and wild-type Ala54/Ala54 as second group. Prevalence of MS with Adult Treatment Panel III definition was 49.7% (373 patients; 24.9% male and 75.1% female), and 50.3% of the patients had no MS (n = 377; 34.2% male and 65.8% female). Prevalence of FABP genotypes was similar in patients with MS (55.5% wild genotype and 44.5% mutant genotype) and without MS (54.6% wild genotype and 45.4% mutant genotype). Prevalence of each criteria of MS was calculated in wild- and mutant-type genotypes, without statistical differences. No differences in anthropometric and biochemical parameters were detected between genotypes in the same group of MS. The finding of our study is the lack of association of the Thr54/Ala54 and Thr54/Thr54 FABP2 genotypes with MS. 相似文献
11.
The intestinal fatty acid-binding protein gene is proposed as a candidate gene for diabetes because the protein it codes is involved in fatty acid absorption and metabolism. This study investigates the association of the Ala54Thr variant of the intestinal fatty acid-binding protein gene on type 2 diabetes mellitus and other related metabolic traits in Asian Indians. Ala54Thr polymorphism was genotyped by using polymerase chain reaction-restriction fragment length polymorphism in unrelated 773 type 2 diabetic and 899 normal glucose-tolerant (NGT) subjects, randomly chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in South India. The Ala54Thr polymorphism was not associated with type 2 diabetes mellitus or obesity. However, genotype-phenotype study revealed that the NGT subjects carrying the Thr54 allele had significantly higher 2-hour plasma glucose (P = .007), glycated hemoglobin (P = .004), 2-hour insulin (P = .027), and fasting low-density lipoprotein cholesterol (P = .032) levels compared with those with the Ala54 allele. Normal glucose-tolerant subjects with Ala54Thr and Thr54Thr genotypes had significantly higher fasting serum triglyceride levels (P = .003) compared with those with Ala54Ala. The subjects were stratified into those with hypertriglyceridemia (serum triglyceride levels >or=150 mg/dL) and those without. The odds ratio for hypertriglyceridemia for the individuals carrying the Ala54Thr genotype was 1.491 (95% confidence interval [CI], 1.22-1.83, P < .0001), and for those carrying the Thr54Thr genotype, it was 1.888 (95% CI, 1.34-2.67; P < .0001). Subjects were also stratified into those with metabolic syndrome (MS) and those without, according to modified Adult Treatment Panel III guidelines. The odds ratio (adjusted for age and sex) for MS for the individuals carrying the Ala54Thr genotype was 1.240 (95% CI, 1.02-1.51; P = .03), whereas for those carrying the Thr54Thr genotype, it was 1.812 (95% CI, 1.28-2.57; P = .001). Carriers of the Thr54 allele have associations with MS and hypertriglyceridemia in this urban South Indian population. 相似文献
12.
Keiji Yoshioka Toshihide Yoshida Akinori Kogure Yasuto Takakura Tsunekazu Umekawa Hitoshi Toda 《Diabetes & Metabolic Syndrome: Clinical Research & Reviews》2010,4(1):18-20
To test the hypothesis whether the Ala54Thr polymorphism of the fatty acid binding protein 2 (FABP2) gene was associated with diabetic nephropathy, we studied a total of 397 Japanese type 2 diabetic patients. The diagnosis of diabetic nephropathy was based on measurements of urinary albumin:creatinine ratio (ACR). We subdivided subjects as those with normoalbuminuria (ACR < 30 mg/g Cr), those with micro- albuminuria (ACR:30–300 mg/g Cr), and those with macroalbuminuria (ACR 3300 mg/g Cr). FABP2 genotypes were determined with a fluorescent allele-specific DNA primer assay system. The results showed that the genotypes of Ala54Thr polymorphism of the FABP2 gene were not significantly different among normo-, micro- and macro-albuminuria groups, suggesting that polymorphism of this gene was not associated with diabetic nephropathy in Japanese type 2 diabetic subjects. 相似文献
13.
Mario L. Salguero Ricardo E. Leon Arturo Santos Sonia Roman Jorge E. Segura-Ortega Arturo Panduro 《Hepatology research》2005,33(4):306-312
Hypertriglyceridemia and dietary lipids have been suggested to modulate the severity of alcoholic liver disease and the progression to alcoholic cirrhosis (AC). The intestinal fatty acid binding protein (IFABP) is the main transporter of dietary fatty acids into the enterocyte and has a genetic polymorphism, FABP2 A54T that has been associated with hypertriglyceridemia. We determined the frequency of the FABP2 gene polymorphism using PCR-RFLP and measured serum triglycerides, HDL, LDL, total lipids and cholesterol in 67 patients with AC and in 124 unrelated healthy individuals. Frequencies of genotypes and alleles were similar between the two groups. The healthy subjects, who were homozygous for the Thr54 genotype had significantly higher mean triglyceride serum concentrations than those homozygous for the Ala54 genotype (P < 0.05). However, AC patients who were homozygous for the Thr54 genotype, had lower mean triglyceride serum concentrations (P < 0.01), and had a significantly longer period of continued alcohol abuse prior to the diagnosis of liver cirrhosis compared to the AC patients homozygous for the Ala54 genotype (P < 0.05).Our data suggests that the polymorphism Thr54 of the FABP2 gene is associated with a later onset of AC in the lower economic status Mexican population studied. 相似文献
14.
T Ishii H Hirose T Kawai K Hayashi H Maruyama I Saito T Saruta 《Metabolism: clinical and experimental》2001,50(11):1301-1307
The present study was performed to investigate the effects of the intestinal fatty acid-binding protein (FABP2) gene Ala54Thr polymorphism and the beta(3)-adrenergic receptor (beta3AR) gene Trp64Arg polymorphism on body mass index (BMI), blood pressure, heart rate, glucose and lipid profiles, and serum leptin level in 196 young men aged 21 to 39 years, 186 older normoglycemic men (fasting plasma glucose [FPG] < 110 mg/dL) aged 40 to 65 years, and 122 older hyperglycemic men, including 77 type 2 diabetic patients. Genomic DNA was extracted from the peripheral blood, and these polymorphisms were assessed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. In the older groups, the beta3AR Arg64-allele frequency tended to be lower and the FABP2 Thr/Thr54 genotype frequency tended to be higher in hyperglycemic patients, although these differences did not reach statistical significance. Also, there were no significant differences in the genotype or allele frequency of either variant between the 27 hyperlipidemic and 204 normolipidemic subjects. In the younger group, there were no significant differences in any of the parameters measured between the genotypes of beta3AR or FABP2. In the older normoglycemic subjects, heart rate was significantly lower (P =.037) in beta3AR Arg64-positive subjects, and FPG was significantly higher in subjects with the FABP2 Thr/Thr genotype than the other genotypes (99.8 +/- 5.6 v 96.5 +/- 5.6 mg/dL, P =.010). In the older hyperglycemic group, the beta3AR Arg64-positive group had significantly lower high-density lipoprotein (HDL) cholesterol and free fatty acid (FFA) levels (P =.024 and P =.043, respectively). There were no synergistic effects of these 2 variants on any measured parameter, but only the FABP2 Thr/Thr genotype was related to a higher FPG in the older normoglycemic men. In conclusion, no major difference was associated with the beta3AR Trp64Arg or FABP2 Ala54Thr polymorphism in terms of type 2 diabetes or hyperlipidemia in young to older Japanese men. However, a slight but significant increase in FPG was observed in older Japanese men with the FABP2 Thr/Thr genotype. 相似文献
15.
Lefevre M Lovejoy JC Smith SR Delany JP Champagne C Most MM Denkins Y de Jonge L Rood J Bray GA 《Metabolism: clinical and experimental》2005,54(12):553-1658
Trans-fatty acids have been implicated as a risk factor for cardiovascular disease and diabetes. In addition, a polymorphism at codon 54 (Ala54Thr) in the fatty acid-binding protein 2 (FABP2) gene has been suggested to modify an interaction between dietary fat and insulin sensitivity. We examined the postprandial metabolic profiles after meals enriched with C18:1trans- relative to a similar meal with C18:1cis-fatty acid in individuals who were either FABP2 Ala54 homozygotes or Thr54 carriers. Moderately overweight men and women ate 2 breakfast test meals, separated by 1 week, each providing 40% of their daily energy requirement and containing 50% of energy as fat. In one meal, 10% of energy was from C18:1trans, and in the other meal, the C18:1trans was replaced with C18:1cis. Metabolic parameters were assessed during an 8-hour period. Insulin and C-peptide levels increased more after the C18:1trans meal, and this was associated with a greater fall in free fatty acids. Postprandial glucose levels and oxidation of fatty acids and carbohydrate were not different between the 2 test meals. The Thr54 allele for FABP2 increased the rise in postprandial glucose but not triacylglycerols. Fractional triacylglycerol synthetic rates were higher after consumption of the C18:1trans meal relative to the C18:1cis meal only in Thr54 carriers. These data show that a single meal enriched with C18:1trans-fatty acids can significantly increase insulin resistance, and that in the presence of the FABP2 Thr54 allele, may contribute to increased partitioning of glucose to triacylglycerols and insulin resistance. 相似文献
16.
Grarup N Andersen MK Andreasen CH Albrechtsen A Borch-Johnsen K Jørgensen T Auwerx J Schmitz O Hansen T Pedersen O 《The Journal of clinical endocrinology and metabolism》2007,92(1):363-366
CONTEXT: The type 2 iodothyronine deiodinase (D2) catalyzes the conversion of T(4) to the active form of thyroid hormone, which is a critical regulator of thermogenesis and glucose metabolism. A Thr92Ala polymorphism in the gene encoding D2 (DIO2) has been reported to associate with insulin resistance. OBJECTIVE: The aim of the present study was to assess the impact of the DIO2 Thr92Ala variant on type 2 diabetes (T2D), obesity, and related quantitative metabolic traits including measures of insulin resistance. Because DIO2 is activated through a beta-adrenergic receptor-dependent pathway, we further hypothesized that variation in the ADRB genes interacts with DIO2 Thr92Ala variant to influence metabolic traits. DESIGN AND PATIENTS: The DIO2 polymorphism was genotyped in a total of 7342 white subjects including 1405 T2D patients. RESULTS: We detected no significant association of the DIO2 Thr92Ala polymorphism with T2D or obesity. We observed nominal significant associations of genotype with increased area under the serum insulin curve during an oral glucose tolerance test (P = 0.03) and elevated fasting plasma glucose (P = 0.02) in homozygous Ala92 allele carriers, the latter strengthened by epistasis with the ADRB2 Gly16Arg variant in a double recessive model (P = 0.004). However, after permutation procedure, performed to correct for multiple hypothesis testing, the associations did not reach study-wide significance. CONCLUSIONS: The DIO2 Thr92Ala variant does not confer an increased risk of T2D, obesity, or insulin resistance. 相似文献
17.
Canani LH Capp C Dora JM Meyer EL Wagner MS Harney JW Larsen PR Gross JL Bianco AC Maia AL 《The Journal of clinical endocrinology and metabolism》2005,90(6):3472-3478
The single-nucleotide polymorphism A/G in the type 2 deiodinase (D2) gene predicts a threonine (Thr) to alanine (Ala) substitution at codon 92 (D2 Thr92Ala) and is associated with insulin resistance in obese patients. Here, this association was investigated in 183 patients with type 2 diabetes mellitus, using homeostasis model assessment. The median fasting plasma insulin in Ala/Ala individuals was significantly higher than in patients with Ala/Thr or Thr/Thr genotypes (19.6 vs. 12.0 vs. 14.8 mIU/ml, respectively; P = 0.004). Assuming a recessive model, the homeostasis model assessment index was higher in the Ala/Ala group when compared with Ala/Thr-Thr/Thr group (8.50 vs. 4.85, P = 0.003). Although this polymorphism has not been associated with changes in D2 kinetics as measured in HEK-293 cells transiently expressing D2 Thr92Ala, we investigated whether such association could be detected in human tissue samples. Remarkably, in thyroid and skeletal muscle samples from subjects homozygous for the Ala allele, D2 velocity was significantly lower than in subjects with Ala/Thr-Thr/Thr genotypes (P = 0.05 and 0.04, respectively). In conclusion, the A/G polymorphism is associated with greater insulin resistance in type 2 diabetes mellitus patients and with lower D2 velocity in tissue samples. These findings suggest that the D2-generated T(3) in skeletal muscle plays a role in insulin resistance. 相似文献
18.
S Boullu-Sanchis F Leprêtre G Hedelin J P Donnet P Schaffer P Froguel M Pinget 《Diabetes & metabolism》1999,25(2):150-156
We studied by PCR-RFLP 6 polymorphisms in these 5 candidate genes: Ala54Thr in the fatty acid binding protein 2 gene (FABP2), A to G substitution in the uncoupling protein type 1 gene (UCP1), Asp905Tyr in the protein phosphatase type 1 gene (PP1G), Trp64Arg in the human beta 3 adrenergic receptor gene (beta 3AR) and 2 RFLP sites of the vitamin D receptor (VDR) gene (VDRTaq1 and VDRApa1). This study was conducted among 89 cases and 100 controls matched according to age, gender and absence of first degree family link (11 triplets with 2 controls for 1 case and 78 pairs with 1 control for 1 case). Cases and controls were taken among a sample of 429 individuals selected for the study of the prevalence of diabetes in this ethnic group from Guadeloupe. By conditional logistic regression analysis, there was a significant relation (p = 0.02) between the Ala54Thr FABP2 polymorphism and Type 2 DM. Multivariate analysis discriminate the FABP2 polymorphism (p = 0.10), a triglyceridemia over 2 g/l (p < 10(-3)) and high blood pressure (p = 10(-2)) as variables associated with Type 2 DM in this population. These findings suggest that FABP2 does not represent a major gene for Type 2 DM in this migrant Indian population living in Guadeloupe, but seems to be related to the metabolic insulin resistance syndrome. 相似文献
19.
Aim: The role of the codon 54 polymorphism of the fatty acid-binding protein 2 (FABP2) gene on fat metabolism has been controversial. Assuming that the effects of the polymorphism were modulated by gender and obesity which were related to lipid and glucose metabolism, we investigated this polymorphism and its effect on fat metabolism according to such factors.
Methods: Subjects were Japanese–Americans (123 men and 126 women) who were diagnosed as non-diabetic by a 75 g oral glucose tolerance test at the baseline.
Results: During approximately 7.8 years, 49 (24 men and 25 women) were diagnosed with type 2 diabetes. In a Cox proportional hazards model, this polymorphism was not a significant variable in the incidence of diabetes in either gender. Amongst non-obese men with the Thr54 allele, there was a significant elevation of triglycerides (TGs) (p = 0.033) compared with alanine (Ala) homozygotes. Women with the Thr54 allele had significantly elevated total cholesterol (p = 0.033) and low-density lipoprotein-cholesterol (LDL-C) (p = 0.023) compared with Ala54 homozygotes.
Conclusions: These results therefore suggested that the effects of the FABP2 polymorphism on TG, LDL-C and body mass index were associated with gender difference and obesity amongst non-diabetic Japanese–American subjects. 相似文献
Methods: Subjects were Japanese–Americans (123 men and 126 women) who were diagnosed as non-diabetic by a 75 g oral glucose tolerance test at the baseline.
Results: During approximately 7.8 years, 49 (24 men and 25 women) were diagnosed with type 2 diabetes. In a Cox proportional hazards model, this polymorphism was not a significant variable in the incidence of diabetes in either gender. Amongst non-obese men with the Thr54 allele, there was a significant elevation of triglycerides (TGs) (p = 0.033) compared with alanine (Ala) homozygotes. Women with the Thr54 allele had significantly elevated total cholesterol (p = 0.033) and low-density lipoprotein-cholesterol (LDL-C) (p = 0.023) compared with Ala54 homozygotes.
Conclusions: These results therefore suggested that the effects of the FABP2 polymorphism on TG, LDL-C and body mass index were associated with gender difference and obesity amongst non-diabetic Japanese–American subjects. 相似文献
20.
Endo K Yanagi H Hirano C Hayakawa Y Hamaguchi H Tomura S 《Journal of atherosclerosis and thrombosis》2001,8(3):80-83
To investigate whether the Ala54Thr polymorphism of the fatty acid binding protein 2 gene is associated with obesity and obesity with dyslipidemia in Japanese schoolchildren, we analyzed 370 children with morbid obesity and 463 control children of normal weight. The allele frequencies did not differ significantly between the control group and the morbidly obese group. The odds ratio (95% confidence interval CI) in obesity of the The54 allele was 1.0 (0.9-1.3). There were no significant differences in obesity index and metabolic characteristics between the two groups. The odds ratio (95% CI) in dyslipidemia of the Thr54 allele was 1.1 (0.8-1.4) in the morbidly obese group. Our data suggested that Ala54Thr polymorphism of the FABP2 gene is not a major contributing factor for obesity and obesity with dyslipidemia in Japanese children. 相似文献