Influence of eNOS haplotypes on the plasma nitric oxide products concentrations in hypertensive and type 2 diabetes mellitus patients.

Endothelial nitric oxide synthase (eNOS) haplotypes are associated with hypertension (HT) in patients with or without type 2 diabetes mellitus (T2DM). We evaluated the association of eNOS genotypes/haplotypes with the plasma concentrations of nitrite/nitrate (NO(x)), which are products of nitric oxide in HT, T2DM, and T2DM+HT patients. We studied eNOS polymorphisms in the promoter region (T-786C), in exon 7 (Glu298Asp), and in intron 4 (b/a) in 98 controls, 68 patients with HT, 66 patients with T2DM, and 86 patients with T2DM+HT. NO(x) concentrations were assessed using a chemiluminescence assay. No differences were found in genotype/allele distribution among groups. Genotypes were not associated with NO(x) concentrations. The "C-Glu-b" haplotype was more common in controls than in HT/T2DM+HT groups (21% versus 9/5%, respectively, P<0.006). This haplotype was more common in HT and T2DM+HT groups among subjects with high (82+/-38 and 90+/-33 microM, respectively) than with low (35+/-7 and 34+/-7 microM, respectively) NO(x) concentrations. Conversely, the "C-Asp-b" haplotype was more common in HT/T2DM+HT groups than healthy (21/21% versus 10%, respectively, P<0.006). The haplotype associated with lower risk of developing hypertension is also associated with higher NO(x) levels among hypertensives. Conversely, the haplotype increasing the risk of developing hypertension is associated with lower NO(x) levels in hypertensives.     

Islet amyloid polypeptide gene promoter polymorphisms are not associated with Type 2 diabetes or with the severity of islet amyloidosis

The over-expression of the islet amyloid polypeptide (IAPP) gene could be a causal factor for islet amyloidosis and beta-cell destruction in Type 2 diabetes (T2DM). An IAPP gene promoter polymorphism, IAPP-132G to A, has been associated with T2DM in Spain. To investigate this polymorphism in other cohorts and in relation to therapy, DNA from 425 T2DM and 279 unrelated, non-diabetic UK subjects (ND) and 102 T2DM and 80 ND Finnish subjects was examined. The relationship of amyloid severity (percent amyloid/islet) to prevalence (number of islets affected) and the association of IAPP-132G/A with amyloid was determined in post-mortem pancreas from 38 T2DM subjects. The -132G/A was not associated with T2DM in the UK cohorts (4.5% T2DM; 3.2% ND) or associated with requirement for insulin therapy by 6 years. The mutation was and undetected in the Finnish samples but a new variant, -166T/C, was identified in 2 Finnish T2DM subjects. -132G/A was found in 2/38 diabetic, amyloid-containing and 3/19 ND, amyloid-free subjects. The islet amyloid severity was linearly correlated with the prevalence in T2DM. The IAPP-132G/A promoter polymorphism is not associated with T2DM, a requirement for insulin therapy or with the degree of islet amyloidosis in cohorts from the UK or Finland.     

Contribution of nitric oxide to cutaneous microvascular dilation in individuals with type 2 diabetes mellitus

Microvascular pathophysiology associated with type 2 diabetes mellitus (T2DM) contributes to several aspects of the morbidity associated with the disease. We quantified the contribution of nitric oxide (NO) to the cutaneous vasodilator response to nonpainful local warming in subjects with T2DM (average duration of diabetes mellitus 7 +/- 1 yr) and in age-matched control subjects. We measured skin blood flow in conjunction with intradermal microdialysis of N(G)-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) or vehicle during 35 min of local warming to 42 degrees C. Microdialysis of sodium nitroprusside (SNP) was used for assessment of maximum cutaneous vascular conductance (CVC). Resting CVC was higher in T2DM subjects at vehicle sites (T2DM: 19 +/- 2 vs. control: 11 +/- 3%maxCVC; P < 0.05); this difference was abolished by l-NAME (T2DM: 10 +/- 1 vs. control: 8 +/- 1%maxCVC; P > 0.05). The relative contribution of NO to the vasodilator response to local warming was not different between groups (T2DM: 46 +/- 4 vs. control: 44 +/- 6%maxCVC; P > 0.05). However, absolute CVC during local warming was approximately 25% lower in T2DM subjects (T2DM: 1.79 +/- 0.15 AU/mmHg; controls: 2.42 +/- 0.20 AU/mmHg; P < 0.01), and absolute CVC during SNP was approximately 20% lower (T2DM: 1.91 +/- 0.12 vs. control: 2.38 +/- 0.13 AU/mmHg; P < 0.01). We conclude that the relative contribution of NO to vasodilation during local warming is similar between subjects with T2DM and control subjects, although T2DM was associated with a lower absolute maximum vasodilation.     

Association between the −11377 C/G and −11391 G/A polymorphisms of adiponectin gene and adiponectin levels with susceptibility to type 1 and type 2 diabetes mellitus in population from the west of Iran,correlation with lipid profile

Adipose tissue, an endocrine organ, secretes bioactive factors including adiponectin. Adiponectin is a protein hormone that enhances insulin sensitivity through increased fatty acid oxidation and inhibition of hepatic glucose production. We assessed the association of the adiponectin promoter region polymorphisms −11391 G/A and −11377 C/G with susceptibility to type 1 (T1DM) and type 2 (T2DM) diabetes mellitus in the population of west Iran. Also, we investigated the effect of adiponectin level and lipid profile on T1DM and T2DM development. In this case-control study, we recruited 189 patients with diabetes (100 T2DM and 89 T1DM) and 161 sex and age-matched unrelated healthy controls. Adiponectin mutations were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the protein level was measured by the enzyme-linked immunosorbent assay. Other biochemical parameters were determined by routine laboratory methods. The G allele of adiponectin gene at −11377 position (C/G) significantly increased the risk of T1DM. With respect to genotype models, codominant (2.97 times), dominant (3.6-fold), and over-codominant (2.9-fold) patients with T1DM who carried −11377 C > G single-nucleotide polymorphisms were significantly susceptible to the development of the disease. A significantly higher level of adiponectin in T1DM was oberved compared with the control group. In contrast, patients with T2DM had lower adiponectin levels compared with healthy controls. The genotype distributions of −11391 G/A polymorphisms were the same for patients with diabetes and control groups. The presence of G allele at −11377 C/G adiponectin gene significantly increased serum adiponectin level and may be a risk factor for T1DM susceptibility among the western Iranian population.     

脂联素基因单核苷酸多态性T45G与湖北汉族人2型糖尿病的遗传关联研究

采用病例.家系对照和随机病例.对照两种设计,分析了603例样本脂联素基因(Adiponectin,APMl)单核苷酸多态性(SNP)rs13061862(T45G)与湖北汉族人群2型糖尿病的相关性.在所有样本中,2型糖尿病病人的G等位基因及GG基因型频率显著高于正常人(G:42.0%比21.7%,P<0.001;GG:13.6%比4.5%,P=0.032);在180个病例.家系对照中,2型糖尿病患者的GG基因型频率显著高于对照组(GG:17.8%比5.6%,P=0.011);在423个随机病例.对照中,2型糖尿病患者GG基因型频率也显著高于对照组(GG:12.2%比3.9%,P=0.025);单因素Logistic回归分析显示,GG基因型是2型糖尿病的危险因子(OR=3.58,95%C/=1.70-7.54).这些结果表明,脂联素基因SNPT45G多态性与湖北汉族人群2型糖尿病的发生发展相关,GG基因型是中国湖北汉族人2型糖尿病的遗传危险因素.     

Short-term flexibility of myocardial triglycerides and diastolic function in patients with type 2 diabetes mellitus

Short-term caloric restriction increases plasma levels of nonesterified fatty acids (NEFAs) and is associated with increased myocardial triglyceride (TG) content and decreased myocardial function in healthy subjects. Whether this flexibility of myocardial TG stores and myocardial function is also present in patients with type 2 diabetes mellitus (T2DM) is yet unknown. Myocardial TG content and left ventricular (LV) ratio between the early (E) and atrial (A) diastolic filling phase (E/A) were determined using magnetic resonance (MR) spectroscopy and MR imaging, respectively, before and after a 3-day very low-calorie diet (VLCD) in 11 patients with T2DM. In addition, we studied patients after a 3-day VLCD combined with the antilipolytic drug acipimox. The VLCD induced myocardial TG accumulation [from 0.66 +/- 0.09% (mean +/- SE, baseline) to 0.98 +/- 0.16%, P = 0.028] and a decrease in E/A ratio [from 1.00 +/- 0.05 (baseline) to 0.90 +/- 0.06, P = 0.002]. This was associated with increased plasma NEFA levels (from 0.57 +/- 0.08 mmol/l at baseline to 0.92 +/- 0.12, P = 0.019). After the VLCD with acipimox, myocardial TG content, diastolic function, and plasma NEFA levels were similar to baseline values. In conclusion, in patients with T2DM, a VLCD increases myocardial TG content and is associated with a decrease in LV diastolic function. These effects were not observed when a VLCD was combined with acipimox, illustrating the physiological flexibility of myocardial TG stores and myocardial function in patients with T2DM.     

Effect of apoC-III gene polymorphisms on the lipoprotein-lipid profile of viscerally obese men

Abdominal visceral adipose tissue (AT) accumulation is associated with an atherogenic metabolic profile that includes increased plasma triglyceride (TG), low HDL cholesterol levels, and an insulin-resistant hyperinsulinemic state. Whereas the apolipoprotein (apo) C-III C3238G gene variant, often referred to as the SstI polymorphism, has been related to variations in plasma TG concentrations, another variation within the insulin responsive element (C-482T) of the apoC-III gene has been associated with greater glucose and insulin responses to an oral glucose tolerance test (OGTT); however, these results were obtained in nonobese individuals. We therefore investigated the effects of three apoC-III gene polymorphisms, namely SstI, C-482T, and T-455C, on fasting plasma lipoprotein-lipid levels and response to a 75 g OGTT in a sample of 122 viscerally obese men (abdominal visceral AT area >or=130 cm(2)). Among the three gene variants that were examined, the SstI variation was the only one found to be associated with hypertriglyceridemia. Indeed, S1/S2 heterozygotes (n = 24) were characterized by increased fasting plasma TG concentrations compared with S1/S1 homozygotes (n = 98) (mean +/- SD: 3.03 +/- 1.58 vs. 2.34 +/- 0.95 mmol/l respectively, P < 0.05). The higher TG concentrations in S1/S2 were associated with the presence of smaller, denser LDL particles compared with S1/S1 subjects (LDL peak particle diameter: 24.8 +/- 0.5 nm vs. 25.1 +/- 0.5 nm respectively, P < 0.05). Furthermore, there was no association between the response to the OGTT and any of the apoC-III gene variants (SstI, T-455C, or C-482T) examined. Results of the present study support the notion of a hypertriglyceridemic effect associated with the apoC-III SstI polymorphism that could modulate the magnitude of the dyslipidemic state in abdominally obese patients.     

Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes

Type 2 diabetes (T2DM) is associated with chronic low-grade inflammation. Adipose tissue (AT) may represent an important site of inflammation. 3T3-L1 studies have demonstrated that lipopolysaccharide (LPS) activates toll-like receptors (TLRs) to cause inflammation. For this study, we 1) examined activation of TLRs and adipocytokines by LPS in human abdominal subcutaneous (AbdSc) adipocytes, 2) examined blockade of NF-kappaB in human AbdSc adipocytes, 3) examined the innate immune pathway in AbdSc AT from lean, obese, and T2DM subjects, and 4) examined the association of circulating LPS in T2DM subjects. The findings showed that LPS increased TLR-2 protein expression twofold (P<0.05). Treatment of AbdSc adipocytes with LPS caused a significant increase in TNF-alpha and IL-6 secretion (IL-6, Control: 2.7+/-0.5 vs. LPS: 4.8+/-0.3 ng/ml; P<0.001; TNF-alpha, Control: 1.0+/-0.83 vs. LPS: 32.8+/-6.23 pg/ml; P<0.001). NF-kappaB inhibitor reduced IL-6 in AbdSc adipocytes (Control: 2.7+/-0.5 vs. NF-kappaB inhibitor: 2.1+/-0.4 ng/ml; P<0.001). AbdSc AT protein expression for TLR-2, MyD88, TRAF6, and NF-kappaB was increased in T2DM patients (P<0.05), and TLR-2, TRAF-6, and NF-kappaB were increased in LPS-treated adipocytes (P<0.05). Circulating LPS was 76% higher in T2DM subjects compared with matched controls. LPS correlated with insulin in controls (r=0.678, P<0.0001). Rosiglitazone (RSG) significantly reduced both fasting serum insulin levels (reduced by 51%, P=0.0395) and serum LPS (reduced by 35%, P=0.0139) in a subgroup of previously untreated T2DM patients. In summary, our results suggest that T2DM is associated with increased endotoxemia, with AT able to initiate an innate immune response. Thus, increased adiposity may increase proinflammatory cytokines and therefore contribute to the pathogenic risk of T2DM.     

PGC-1α Thr394Thr and Gly482Ser variants are significantly associated with T2DM in two North Indian populations: a replicate case-control study

The recent observations that Peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1A) is responsible for the induction of reactive oxygen species (ROS) detoxifying agents and that ROS triggers insulin resistance, support the role that this gene could play in the onset of Type 2 diabetes mellitus (T2DM). Two PGC1A variants Thr394Thr (rs2970847) and Gly482Ser (rs8192673) were genotyped in 822 subjects (351 T2DM cases and 471 controls) from two North Indian populations, represented as Group 1 (Kashmir population) and Group 2 (Punjab and Jammu population). Both Groups 1 and 2 showed a significant association of Thr394Thr variant with T2DM after applying Bonferroni corrections (P = 0.001 and 0.012, respectively). Logistic regression analysis for Thr394Thr susceptible genotypes together (rs2970847 G/A and A/A) conferred a 1.89-(95%CI 1.25–2.85) fold higher risk for T2DM in Group 1 and 1.81-(95%CI 1.19–2.78) fold risk in Group 2. The susceptible, Ser482 (rs8192673 G/A and A/A) genotypes, gave a 2.04 (95%CI 1.47–3.03) fold higher risk for T2DM in Group 1. Mitochondrial genotype backgrounds observed in association with T2DM (Bhat et al. 2007), when studied in combination with PGC1A variants, showed an increased prevalence in controls with mt10398G and 16189T along with G/G genotype background at the two polymorphic loci of PGC1A. These observations suggest that the two genotype backgrounds together could provide protection against T2DM. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. An erratum to this article is available at .     

MDM2 SNP309 is associated with endometrial cancer susceptibility: a meta-analysis

Epidemiological studies have investigated the association between MDM2 promoter SNP 309 (T/G) and endometrial cancer susceptibility. However, the results are still controversial. To obtain a more precise estimate of the relationship, we conducted a meta-analysis of 1,001 cases and 1,889 controls from 6 published case-control studies (one of five articles contains two studies) to estimate the effect of SNP309 on endometrial cancer risk. The strength of association between MDM2 SNP309 and endometrial cancer susceptibility was assessed by calculating pooled odds ratios (ORs) with 95% confidence intervals (CIs). When all the eligible studies were pooled in the meta-analysis, we found that elevated endometrial cancer risk was significantly associated with GG variant genotype, however, heterozygous genotype TG seemed to be only a minor modifier on endometrial cancer risk (for GG vs. TT, OR?=?1.54, 95% CI?=?1.21-1.95, P?=?0.0004; for TG vs. TT, OR?=?0.96, 95% CI?=?0.81-1.14, P?=?0.66; for dominant model, OR?=?1.09, 95% CI?=?0.93-1.29, P?=?0.29; for recessive model, OR?=?1.65, 95% CI?=?1.33-2.04, P?相似文献   

The interleukin-6 (-174) G/C promoter polymorphism is associated with type-2 diabetes mellitus in Native Americans and Caucasians

Chronic low-grade activation of the immune system may play a role in the pathogenesis of type-2 diabetes mellitus (T2DM). Interleukin-6 (IL6), a powerful inducer of hepatic acute phase response, has been implicated in the etiology of insulin resistance and T2DM. Recently, an IL6 promoter polymorphism (G/C) at position -174 was found to be associated with measures of insulin sensitivity. Because we have previously found an association between high IL6 levels and insulin resistance in both Pima Indians - a population with high rates of insulin resistance and T2DM - and Caucasians, we aimed to assess whether the IL6 promoter polymorphism is associated with T2DM in these populations. We genotyped the IL6 (-174) G/C polymorphism using pyrosequencing in 463 Native Americans and by PCR-RFLP in 329 Spanish Caucasians. Among the Spanish Caucasian subjects, there was a significant difference in genotypic distribution between diabetic and non-diabetic subjects (P=0.028); the GG genotype was more common in diabetic (0.40) than in non-diabetic (0.29) subjects. The G allele was much more frequent in the Native American sample, and among a sample of 143 cases and 145 controls, the GG genotype was significantly more common in diabetic subjects (P=0.019). When this sample population was stratified according to ethnic heritage, all 211 subjects who were of full Pima Indian heritage had the GG genotype, whereas in the 77 American Indian subjects with non-Pima admixture, T2DM was associated with IL6 genotype (P=0.001). These findings are consistent with a role for genetic determinants of inflammation in the development of T2DM in both Native Americans and Caucasians.     

A systematic review and meta-analysis of the relationship between lipoprotein lipase Asn291Ser variant and diseases

This systematic review attempted to summarize the associations between the Asn291Ser variant in the lipoprotein lipase (LPL) gene and dyslipidemia, the risk of type 2 diabetes mellitus (T2DM), and coronary heart disease (CHD). In addition, the relationships between the Asn291Ser variant and other metabolic diseases such as obesity and high blood pressure were also investigated in this systematic review. We systematically reviewed the literature by means of a meta-analysis. Twenty-one articles, including 19,246 white subjects, were selected for this meta-analysis. The summary standardized mean difference (SMD) of plasma triglyceride (TG) for carriers compared with noncarriers of the Asn291Ser variant was 3.23 (P < 0.00001). The summary SMD of plasma HDL-cholsterol (HDL-C) for carriers compared with noncarriers of the Asn291Ser variant was -3.42 (P < 0.0001). The summary SMD of the association of the Asn291Ser variant with plasma TG increased with increasing age and weight gain. Significant interactions between the LPL Asn291Ser variant and fasting glucose, T2DM, and CHD were seen (P = 0.02, 0.04, and 0.01, respectively). No significant interactions were seen between the LPL Asn291Ser variant and body mass index, waist-hip ratio, and blood pressure (P > 0.05). This meta-analysis indicates that the Asn291Ser variant in the LPL gene is a risk factor for dyslipidemia, characterized by hypertriglyceridemia and low HDL-C levels. And the Asn291Ser variant in the LPL gene predisposes to more severe dyslipidemia with increasing age and weight gain. Also, this meta-analysis shows that the LPL Asn291Ser variant is associated with CHD and T2DM.     

The -308 polymorphism in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene and ex vivo lipopolysaccharide-induced TNF-alpha expression in patients with aggressive periodontitis and/or type 1 diabetes mellitus

Several single-nucleotide polymorphisms (SNPs) have been identified in the TNF-alpha gene promoter. The transition G-->A at position -308 generates the TNF-alpha1 (G/G) and TNF-alpha2 (G/A or A/A) alleles, where the polymorphic TNF-alpha2 allele is associated with a high, in vitro TNF-alpha expression and an increased susceptibility to diverse illnesses. Here we study the association of the -308 TNF-alpha SNP with the susceptibility for developing aggressive periodontitis (AP), AP combined with type 1 diabetes mellitus (DM) and DM. We also explore the TNF-alpha capability expression and the presence of the -308 polymorphism. For this purpose we recruited 27 individuals with AP (AP+ group), 27 individuals with AP combined with DM (AP+/DM+ group), and 27 individuals with DM without signs of periodontitis upon clinical examination (DM+ group). The control group was comprised of 30 subjects. Genotyping for TNF-alpha promoter was performed by PCR-RFLP analysis. For TNF-alpha expression we used a blood culture system.     

A Triglyceride‐Raising APOA5 Genetic Variant Is Negatively Associated With Obesity and BMI in the Chinese Population

Apolipoprotein A‐V (apo A‐V) exerts a potent triglyceride (TG)‐lowering effect through enhanced intravascular TG‐hydrolysis with increased uptake of TG‐derived free fatty acids into muscle and adipose tissue. Genetic variants in the APOA5 gene were strongly associated with plasma TG concentrations. The aim of this study was to examine whether APOA5 genetic variation was associated with obesity. We genotyped the missense c.553 G>T polymorphism (p.G185C) in the APOA5 gene in 1,085 Chinese (333 obese subjects and 752 nonobese controls). We analyzed the association between the c.553 G>T polymorphism and obesity and related metabolic phenotypes. The T allele at the c.553 G>T polymorphism was associated with higher plasma TG concentrations. Each additional T allele was associated with an increased TG concentration of 53.5 mg/dl (95% confidence interval (CI) 29.6–76.0, P < 0.0001). However, the T allele was associated lower risk of obesity (odds ratio (OR), 0.48; 95% CI 0.32–0.73, P = 0.0004). Each additional copy of the T allele was associated with a BMI decrease of 0.73 kg/m² (95% CI 0.26–1.16, P = 0.002), equivalent to 2.11 kg in a person 1.7 m tall. We may then conclude that the TG‐raising APOA5 genetic variant was associated with a decrease in BMI and reduced risk of obesity in the Chinese population.     

Paraoxonase 1 gene polymorphisms and enzyme activities in diabetes mellitus

Paraoxonase 1 (PON1), an antioxidant enzyme closely associated with HDL (high-density lipoproteins), preserves LDL (low-density lipoproteins) against oxidation. Less protection may be therefore supposed by decreased PON1 activity. This study was undertaken to investigate the association of PON1 gene polymorphisms with diabetic angiopathy and to evaluate the relationship of these polymorphisms with PON1 activity. Total of 86 Type 1 (T1DM) and 246 Type 2 (T2DM) diabetic patients together with 110 healthy subjects were examined. DNA isolated from leukocytes was amplified with polymerase chain reaction (PCR) followed by restriction enzyme digestion. The products were analyzed for L55M and Q192R polymorphisms in coding region and for -107 C/T and -907 G/C in promotor sequence of PON1. Serum enzyme activity was measured spectrophotometrically. Significant differences were found between T1DM or T2DM and control persons in L55M polymorphism (allele M more frequent in T1DM and T2DM vs. controls, p<0.05) and Q192R polymorphism (R allele less frequent in T1DM and T2DM vs. controls, p<0.01) of the PON1 gene. Serum PON1 activity was significantly decreased in T1DM (110+/-68 nmol/ml/min) and T2DM patients (118+/-69 nmol/ml/min) compared to the control persons (203+/-58 nmol/ml/min), both p<0.01. The presence of MM and QQ genotypes was accompanied by lower PON1 activity than of LL and RR genotypes (p<0.05), respectively. Better diabetes control was found in patients with LL than with MM genotypes and similarly in RR genotype than QQ genotype with p<0.05. Significantly different allele frequencies were found in diabetic patients with macroangiopathy than in those without it (M: 0.59 vs. 0.44. R: 0.12 vs. 0.19, p<0.01). The association of PON1 polymorphisms, lower PON1 activity and poorer diabetes control found in patients with macroangiopathy further support the idea of genetic factors contributing to the development of vascular disorders in diabetes.     

Preliminary evidence of FABP2 A54T polymorphism associated with reduced risk of type 2 diabetes and obesity in women from a German cohort.

The T54 variant of the FABP2 gene has shown an association with the insulin resistance syndrome in some, but not all, studies. Here, we tested the hypothesis that the association between FABP2 A54T genotype and type 2 diabetes (T2DM) is confounded by body mass index (BMI) and is different between the two genders. 192 incident cases of T2DM and 384 sex- and age-matched controls were taken from the EPIC-Potsdam study cohort. Logistic regression analyses revealed that BMI was a strong confounder for diabetes risk association among women. When adjusted for BMI, the homozygous T54 variant was significantly associated with reduced risk of T2DM in women (OR = 0.24, 95 %CI: 0.07 - 0.82), but not in men in the co-dominant inheritance model. Accordingly, HbA (1c) values were significantly lower in women carrying two T54 alleles with BMI regarded as covariate. While accounting for potentially confounding effects, linear trends of increased BMI and leptin values were observed in women according to the presence of T54 alleles. The interaction term (p = 0.04) of continuous BMI and T54-coding genotypes suggested that the T54 variant is an effect-modifier for BMI in females. We conclude that the T54 allele of FABP2 A54T is associated both with higher BMI and reduced risk of T2DM in women from the German EPIC-Potsdam study.