Interleukin 1 beta −511 C/T gene polymorphism and susceptibility to febrile seizures: a meta-analysis

One previous meta-analysis found no evidence that interleukin 1 beta (IL-1β) −511 gene polymorphism was associated with febrile seizures (FS) by pooling a limited number of studies. However, it is necessary for the meta-analysis to reevaluate the relationship with more recent findings. Electronic databases were systematically searched for studies published before June 2011. Pooled odds ratios (OR) and 95% confidence interval (CI) were estimated by means of a genetic model free approach. Subgroup and sensitivity analyses were also performed. All statistical analyses were conducted using Stata 9.0. A total of eight studies, 728 FS cases and 1,223 controls, met the selection criteria. The results show a significant association between IL-1β −511 C/T gene polymorphism and FS (recessive genetic model TT vs. CC + CT: OR = 1.361, 95% CI: 1.065–1.738, P = 0.014). Subgroup analyses show a significant association in Asia (OR = 1.394, 95% CI: 1.005–1.935, P = 0.047), but not in Europe (OR = 1.387, 95% CI: 0.750–2.565, P = 0.298). IL-1β −511 C/T gene polymorphism may play a role in susceptibility to FS, especially in Asia. Geographic differences may be a critical factor in the risk of FS.     

Genetic variants in transforming growth factor-β gene (TGFB1) affect susceptibility to schizophrenia

Immense body of evidence indicates that dysfunction of immune system is implicated in the etiology of schizophrenia. The immune theory of schizophrenia is supported by alterations in cytokine profile in the brain and peripheral blood. Given the strong genetic background of schizophrenia, it might be assumed that aberrant production of cytokines might be the consequence of genetic factors. This study aimed at investigating the association between schizophrenia susceptibility and selected functional polymorphisms in genes encoding cytokines including: interleukin-2 (IL2 ?330T>G, rs2069756), interleukin-6 (IL-6 ?174G>C, rs1800795), interferon-γ (IFNG +874T>A, rs2430561) as well as for the first time transforming growth factor-β1 (TGFB1 +869T>C, rs1800470 and +916G>C, rs1800471). We recruited 151 subjects with schizophrenia and 279 controls. There was a significant difference in the genotype distribution and allelic frequency of the TGFB1 +869T>C between patients with schizophrenia and healthy controls (p < 0.05). The risk of schizophrenia was more than two-fold higher in carriers of T allele (CT+TT genotypes) than individuals with CC genotype. Given documented gender differences in incidence of schizophrenia, we conducted separate analyses of male and female participants. We have shown that the association was significant in females, while in males it reached a trend toward statistical significance. To the best of our knowledge, it is the first report showing the association between TGFB1 +869T>C polymorphism and schizophrenia.     

The importance of ERα and ERβ gene polymorphisms in PCOS

Estrogens act through binding to estrogen receptor α (ERα) and β (ERβ). Studies in knockout mice have shown that the absence of ERα leads to the polycystic ovary syndrome (PCOS) phenotype. Furthermore, the expression of ERβ gene is lower in follicles derived from women with PCOS compared with healthy women. The aim of this study was to investigate the importance of ERα and ERβ gene polymorphisms in PCOS. A cohort of 180 women with PCOS and 140 healthy controls were recruited, and the PvuII and XbaI polymorphisms of ERα, as well as, the AluI and RsaI polymorphisms of ERβ were genotyped. No difference was found in the distribution of these polymorphisms between patients and healthy controls. However, in PCOS women, carriers of TC and TT genotypes of PvuII polymorphism had lower fasting glucose to insulin ratio compared with carriers of CC genotype (p = 0.029). In addition, the presence of AA genotype of XbaI polymorphism was associated with lower levels of follicle-stimulating hormone (FSH) compared with the presence of AG and GG genotypes (p = 0.03). The association of ERα polymorphisms with insulin resistance indices and FSH levels emphasizes the importance of ERα as a genetic modifier of the PCOS phenotype.     

XRCC1 gene polymorphisms and lung cancer susceptibility: a meta-analysis of 44 case–control studies

X-ray repair cross-complementing group 1 gene (XRCC1) has been implicated in risk for lung cancer. However, the results from different studies remain controversial. In this meta-analysis, we have assessed 44 published case-control studies regarding associations of lung cancer risk with three common polymorphisms, codon 194, codon 280 and codon 399, and -77 T?>?C in the promoter region of XRCC1. The results in total population showed that the risk for lung cancer was increased among the variant homozygote Trp/Trp of codon 194 polymorphism, compared with the wild type Arg/Arg (OR: 1.19; 95?% CI 1.01-1.39), and the variant genotype CC of -77 T?>?C polymorphism showed a significantly increased risk of developing lung cancer, compared to wild-type genotype TT (OR: 1.91; 95?% CI 1.24-2.94). However, no associations were found between lung cancer risk and codon 280, codon 399. In the subgroup analyses by ethnicity, the OR for the variant homozygote Trp/Trp of codon 194 was 1.21(95?% CI 1.02-1.43) for Asian. When stratified by source of control, we found a protective effect of codon 194 Arg/Trp genotype (OR: 0.87; 95?% CI 0.77-0.98) and risk effect of codon 399 combined Arg/Gln?+?Gln/Gln variant genotype (OR: 1.09; 95?% CI 1.01-1.18) for lung cancer on the basis of hospital control. Subgroup analyses by histological types of lung cancer indicated that the heterozygote Arg/Trp in codon 194 could decrease and the combined variant genotype Arg/Gln?+?Gln/Gln in codon 399 could increase the risk of non-small cell lung cancer (OR: 0.69; 95?% CI 0.57-0.85 and OR: 1.14; 95?% CI 1.04-1.24). In conclusion, this meta-analysis has demonstrated that codon 194, codon 399 and -77 T?>?C polymorphisms of XRCC1 gene might have contributed to individual susceptibility to lung cancer. To further evaluate effect of XRCC1 polymorphisms, gene-gene interaction and gene-environment interaction on lung cancer risk, a single large sample size study with thousands of subjects is required to get conclusive results.     

Association of gene polymorphisms in MYH11 and TGF-β signaling with the susceptibility and clinical outcomes of DeBakey type III aortic dissection

To investigate the association of myosin heavy chain protein 11 (MYH11) and transforming growth factor β signaling-related gene polymorphisms with the susceptibility of DeBakey type III aortic dissection (AD) and its clinical outcomes. Four single-nucleotide polymorphism (SNPs) (MYH11 rs115364997, rs117593370, TGFB1 rs1800469, and TGFBR1 rs1626340) were analyzed in patients with DeBakey III AD (173) and healthy participants (335). Gene–gene and gene–environment interactions were evaluated using generalized multifactor dimensionality reduction. The patients were followed up for a median of 55.7 months. MYH11 rs115364997 G or TGFBR1 rs1626340 A carriers had an increased risk of DeBakey type III AD. MYH11, TGFB1, TGFBR1, and environment interactions contributed to the risk of DeBakey type III AD (cross-validation consistency?=?10/10, P?=?0.001). Dominant models of MYH11 rs115364997 AG?+?GG genotype (HR?=?2.443; 95%CI: 1.096–5.445, P?=?0.029), TGFB1 rs1800469 AG?+?GG (HR?=?2.303; 95%CI: 1.069–4.96, P?=?0.033) were associated with an increased risk of mortality in DeBakey type III AD. The dominant model of TGFB1 rs1800469 AG?+?GG genotype was associated with an increased risk of recurrence of chest pain in DeBakey type III AD (HR?=?1.566; 95%CI: 1.018–2.378, P?=?0.041). In conclusions, G carriers of MYH11 rs115364997 or TGFB1 rs1800469 may be the poor prognostic indicators of mortality and recurrent chest pain in DeBakey type III AD. The interactions of gene–gene and gene–environment are associated with the risk of DeBakey type III AD.

     

Association of polymorphisms in transforming growth factor-β receptors with susceptibility to gastric cardia adenocarcinoma

Both transforming growth factor-β receptor I (TGFBR1) and receptor II (TGFBR2) are serine/threonine kinases and play important roles in TGF-β/Smads signal pathway. The case–control study was performed to evaluate the possible association of Int7G24A and *6A polymorphisms of TGFBR1 and G-875A polymorphism of TGFBR2 with susceptibility to gastric cardia adenocarcinoma (GCA) in a population of North China. Polymerase-chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and PCR methods were used respectively to detect the genotype of Int7G24A, *6A and G-875A in 468 GCA and 584 healthy controls. Immunohistochemistry method was used to determine the protein expression of TGFBR1 and TGFBR2. Family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing GCA. There were no differences in the genotype distribution of TGFBR1 *6A polymorphism among cases and controls. However, A allele of Int7G24A significantly elevated the risk of developing GCA (adjusted OR = 1.34, 95% CI 1.03–1.87) and A allele of G-875A significantly decreased the risk of developing GCA (adjusted OR = 0.73, 95% CI 0.49–0.92). When stratified for TNM stage, A allele of Int7G24A and G-875A allele carriers had a 1.41-fold (95% CI 1.05–1.98) increased and a 0.70-fold (95% CI 0.47–0.92) decreased risk of stage III and IV gastric cardia adenocarcinoma. The protein expression of TGFBR1 and TGFBR2 in GCA was not correlated with genotypes of them. In conclusions, TGFBR1 Int7G24A and TGFBR2 G-875A polymorphisms may play important roles in the risk of GCA in North China.     

Association of IL1β and IL4 gene polymorphisms with nasal polyps in a Polish population

Imbalance between proinflammatory and anti-inflammatory cytokines may regulate the inflammatory reaction in the nasal polyps. Polymorphisms in the regulatory regions of the cytokines genes may influence their expression. The aim of this study was to investigate the relationship between an IL-1β and IL-4 promoter polymorphisms and nasal polyps. The C-511T promoter polymorphism of the IL-1β gene and C-590T promoter polymorphism of the IL-4 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 208 Polish patients with nasal polyps and 200 healthy Polish subjects. The risk of susceptibility to NP was significantly higher in patients with NP who had ?511 T/T genotype of IL1β than in controls (OR 3.07; 95 % CI 1.18–7.99). No statistically significant differences were found between NP patients and the control group with regard to genotype distribution and allele frequencies of C/T polymorphism of IL4 gene. Our study demonstrated that the TT genotype for C-511T mutation associated with the risk of developing NP in a Polish population.     

CTLA-4 polymorphisms and susceptibility to Behcet’s disease: a meta-analysis

The aim of this study was to explore whether cytotoxic T lymphocyte antigen-4 (CTLA-4) polymorphisms confer susceptibility to Behcet's disease (BD). A meta-analysis was conducted on the associations between the CTLA-4 +49 A/G, -318 C/T, CT60 A/G polymorphisms and BD using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 8 separate comparison studies on BD were considered in the meta-analysis. Meta-analysis of the CTLA-4 +49 A/G polymorphisms showed no association between BD and the CTLA-4 +49 G allele in all study subjects (odds ratio [OR] = 0.780, 95 % confidence interval [CI] = 0.491-1.240, p = 0.294). Moreover, stratification by ethnicity indicated no association between the CTLA-4 +49 G allele and BD in Turkish population. No association was found between BD and the CTLA-4 +49 A/G polymorphisms using recessive or dominant models or contrast of homozygotes. No association was found between BD and the CTLA-4 -318 C/T or CT60 A/G polymorphisms. This meta-analysis showed that no association was found between CTLA-4 +49 A/G, -318 C/T or CT60 A/G polymorphisms and BD.     

The association between IFN-γ and IL-4 genetic polymorphisms and childhood susceptibility to bronchial asthma

The present study aims to investigate the association between the genetic polymorphisms of interferon (IFN)-γ and interleukin (IL)-4 with childhood susceptibility to asthma and the levels of IFN-γ, IL-4, and immunoglobulin (Ig) E among asthmatic children. A total of 100 asthmatic children and 122 control children were enrolled in the present study. The genotypes of the IFN-γ gene at the − 179G/T locus and the IL-4 gene at the − 33C/T and − 589C/T loci were detected using polymerase chain reaction with restriction fragment length polymorphism. The IFN-γ gene at the + 874A/T locus and the IFN-γ CA repeats were tested using allele-specific and capillary electrophoresis, respectively, whereas the IFN-γ, IL-4, and total IgE levels were measured using enzyme-linked immunosorbent assays. The 100 asthmatic children and the 122 control children were all GG homozygous in the − 179 locus of the IFN-γ gene, which shows that the IFN-γ gene is not mutated at the − 179 locus. No significant differences were found in terms of genotypic and allelic frequency distribution in the IFN-γ gene or the CA repeat at the + 874A/T locus between the asthmatic children and the control (P > 0.05). An association was found between the polymorphism of the IFN-γ gene at + 874A/T and IFN-γ levels. IFN-γ expression was lower among patients with the AA genotype than those with the AT genotype (P < 0.05); the genotypic and allelic frequency distributions of the IL-4 gene at − 33C/T and − 589C/T were significantly different between the asthmatic children and the control (P < 0.05). The levels of IL-4 and IgE among children with TT genotype at the − 33 and − 589 loci were higher than those with the CT genotype, but only the polymorphism at − 33C/T was associated with IL-4 levels (P < 0.05). The polymorphisms of the IFN-γ gene at + 874A/T or the CA repeats are not correlated with susceptibility to asthma. Thus, the polymorphism at + 874A/T is correlated with IFN-γ level. The TT genotypes of the IL-4 gene at the − 33 and − 589 loci are associated with asthma susceptibility in children, and polymorphism at the − 33 locus may be associated with IL-4 level.     

Interleukin-1β and receptor antagonist (IL-1Ra) gene polymorphisms and the prediction of the risk of end-stage renal disease

Abstract

Cytokines play an important role in the pathogenesis of kidney disease and its progression to end-stage renal disease (ESRD). Inflammation is regulated by the genes of the interleukin 1 (IL-1) gene cluster. Therefore, it was hypothesized that a polymorphism in this gene cluster may be associated with the risk of ESRD. Polymorphisms in the IL-1 gene cluster were examined in a cohort of 222 ESRD patients and 206 controls of similar ethnicity. These individuals were genotyped for IL-1 β (promoter –511 and exon-5 +3953) genes and a variable number of tandem repeats (VNTR) in the IL-1 receptor antagonist gene (IL-1Ra). There was significant difference in genotype frequencies between ESRD patients and control group for IL-1β (promoter region and exon-5) and IL-1Ra gene polymorphism (p<0.001, 0.006 and?<?0.001, respectively). A significant difference was observed in IL-1Ra for 1/1 (410/410) and 1/2 (410/240) genotypes, and the risk for ESRD was higher in those carrying the 1/1 genotype (p=0.014, OR?=?1.692, and p<0.001, OR?=?0.163). Also identified was a novel, rare allele of a single copy of 86 bp in ESRD patients as compared with the controls. The haplotype ‘T-E2-1’ frequency distribution between patients and controls revealed greater than threefold risk (p=0.001, OR?=?3.572, 95% CI?=?1.589–8.032). Genetic linkage between the IL-1β promoter region and exon-5 and between the IL-1β promoter and IL-1Ra of IL-1 gene demonstrated a strong association among the variants in controls (D′?=?0.42, p<0.001, and D′?=?0.39, p=0.001). Thus, the three polymorphisms within the IL-1 cluster are associated with ESRD. This finding is perhaps one of the strongest associations between genotype and ESRD reported, and it suggests that the IL-1 gene cluster affects the risk of development of ESRD.     

IL-1β (−511T/C) gene polymorphism not IL-1β (+3953T/C) and LT-α (+252A/G) gene variants confers susceptibility to visceral leishmaniasis

Lymphotoxin-α (LT-α) and interleukin-1beta (IL-1β) are proinflammatory cytokines playing important roles in immunity against Leishmania infection and the outcome of the disease. As cytokine productions are under the genetic control, this study tried to find any probable relationship between these cytokine gene polymorphisms and the susceptibility to visceral leishmaniasis in Iranian pediatric patients. Ninety-five pediatric patients involved with visceral leishmaniasis and 128 non-relative healthy people, from the same area as the patients, were genotyped for LT-α (+252A/G) and IL-1β (+3953T/C and −511T/C) gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP). There was not found any significant differences in allele and genotype frequencies of LT-α (+252A/G) and IL-1β (+3953) among the study groups. However, the frequency of IL-1β −511TT genotype was higher in the controls (P = 0.0004) while the frequency of IL-1β −511CC genotype and C allele were higher in the patients (P = 0.008 and P = 0.00006, respectively). Furthermore, IL-1β CC (−511/+3953) haplotype was more frequent in VL patients compared with the controls (P = 0.0002) and the distribution of TT haplotype was higher in the controls compared with the patients (P = 0.003). In conclusion, based on the results, IL-1β −511C allele, CC genotype and CC (−511/+3953) haplotype could be considered as the susceptibility factors for visceral leishmaniasis while IL-1β −511TT genotype, T allele and TT haplotype (−511/+3953) might be counted as the influential factors for resistance to the disease.     

Genetic polymorphisms in the DNA repair gene XRCC1 and susceptibility to glioma in a Han population in northeastern China: A case–control study

Background

Several single nucleotide polymorphisms (SNPs) in the X-ray cross-complementing group 1 (XRCC1) gene have been shown to influence DNA repair and to modify cancer susceptibility. To investigate the role of these loci further, we examined the association of three XRCC1 polymorphisms with the risk of gliomas in a Han population in northeastern China.

Methods

Using a PCR–RFLP method, XRCC1 Arg194Trp, Arg280His and Arg399Gln were genotyped in 624 glioma patients and 580 healthy controls.

Results

Significant differences in the distribution of the Arg399Gln allele were detected between glioma patients and healthy controls by a logistic regression analysis (OR = 1.35, 95%CI 1.17–1.68, P = 0.001). Our data also revealed that the Arg399Gln variant (allele A) carriers had an increased glioma risk compared to the wild-type (allele G) homozygous carriers (OR = 1.40, 95%CI 1.12–1.76, P = 0.003).

Conclusions

These results suggest that the XRCC1 Arg399Gln might influence the risk of developing glioma in a Han population in northeastern Chinese.     

β1 adrenergic receptor polymorphisms and heart failure: a meta-analysis on susceptibility, response to β-blocker therapy and prognosis

Aims

The risk stratification of patients for heart failure (HF) remains a challenge, as well as the anticipation of the response to β-blocker therapy. Since the pivotal role of β1 adrenergic receptor (β1-AR) in HF, many publications have studied the associations between the β1-AR polymorphisms (Ser49Gly and Arg389Gly) and HF, with inconsistent results. Thus, we performed a meta-analysis of studies to evaluate the impact of β1-AR polymorphisms on susceptibility to HF, the response to β-blocker therapy and the prognosis of HF.

Methods and Results

Electronic databases were systematically searched before August 2011. We extracted data sets and performed meta-analysis with standardized methods. A total of 27 studies met our inclusion criteria. It was found that in East Asians, the Gly389 allele and Gly389 homozygotes significantly increased the HF risk, while the Gly389 allele and Gly389 homozygotes trended to decrease the risk of HF in whites. With the similar reduction of heart rate, overall, the Arg389 homozygotes showed a better response to β-blocker therapy. Furthermore, the Arg389 homozygotes were significantly associated with better LVEF improvement in East Asians and a mixed population. And in white people, the Arg389 homozygotes made a greater LVESd/v improvement and trended to be associated with better LVEDd/v improvement. However, the prognosis of Arg389 homozygotes HF patients was similar to those with Gly389 carriers. The Ser49Gly polymorphism did not impact the risk or prognosis of HF.

Conclusion

Based on our meta-analysis, the Gly389 allele and Gly389 homozygotes were risk factors in East Asians while trending to protect whites against HF. Furthermore, Arg389 homozygote is significantly associated with a favorable response to β-blocker treatment in HF patients. However, neither of the two polymorphisms is an independent predictor of the prognosis of HF.     

Polymorphisms in the interleukin-4 receptor α chain gene influence susceptibility to HIV-1 infection and its progression to AIDS

Interleukin (IL) 4 is a key T helper-2 cytokine that downregulates and upregulates CCR5 and CXCR4, respectively, the main coreceptors for HIV. Our objective is to investigate whether single-nucleotide polymorphisms (SNPs) in the IL-4 receptor α chain gene (IL4RA) affect HIV infection and its progression to AIDS. The I50V SNP in exon 5 and the haplotypes of six SNPs in exon 12 (E375A, C406R, S411L, S478P, Q551R, and V554I) were studied by polymerase chain reaction and sequencing in 30 HIV⁺ long-term nonprogressors (LTNP), 36 HIV⁺ typical progressors (TP), 55 highly exposed but uninfected individuals (EU), 25 EU-sexuals (EU-Sex; mostly women) and 30 EU-hemophiliacs (EU-Hem; hepatitis C virus⁺), and 97 healthy controls (HC), all Caucasians and lacking CCR5Δ32 homozygosity. V50 homozygosity was increased in LTNP (44%) compared with the other groups [p=0.005; relative risk ratio=3.4, 95% confidence interval (CI)=1.12–10.6, p=0.03]. The most common (C) exon 12 haplotype, ECSSQV, predominated in all groups, but uncommon (U) haplotypes were increased in HIV⁺ individuals (n=64), especially in those (51 of 64) infected via parenteral exposure (35.3%) compared with HC (20.4%) and EU-Hem (18.4%) [p=0.01; odds ratio (OR)=2.14, 95% CI=1.25–3.67, p=0.01]. EU-Sex also had an increased frequency of U-haplotypes (34.8%) (OR=2.10, 95% CI=1.03–4.21, p=0.01) as well as an increased frequency of CU + UU genotypes (60.9%) compared with HC (38.2%) and EU-Hem (26.6%) (p=0.043). Distributions of genotypes fitted Hardy–Weinberg equilibrium. Data suggest that V50 homozygosity associates with slow progression and that exon 12 U-haplotypes might be associated with both susceptibility to infection via parenteral route and resistance to infection via sexual exposure. Further studies are required to confirm these findings.     

CYP1A1, GSTM1 and GSTT1 polymorphisms and lung cancer: a pooled analysis of gene–gene interactions

Gene–environment interactions have been extensively studied in lung cancer. It is likely that several genetic polymorphisms cooperate in increasing the individual risk. Therefore, the study of gene–gene interactions might be important to identify high-susceptibility subgroups. GSEC is an initiative aimed at collecting available data sets on metabolic polymorphisms and the risks of cancer at several sites and performing pooled analyses of the original data. Authors of published papers have provided original data sets. The present paper refers to gene–gene interactions in lung cancer and considers three polymorphisms in three metabolic genes: CYP1A1, GSTM1 and GSTT1. The present analyses compare the gene–gene interactions of the CYP1A1*2A, GSTM1 and GSTT1 polymorphisms from studies on lung cancer conducted in Europe and the USA between 1991 and 2000. Only Caucasians have been included. The data set includes 1466 cases and 1488 controls. The only clear-cut association was found with CYP1A1*2A. This association remained unchanged after stratification by polymorphisms in other genes (with an odds ratio [OR] of approximately 2.5), except when interaction with GSTM1 was considered. When the OR for CYP1A1*2A was stratified according to the GSTM1 genotype, the OR was increased only among the subjects who had the null (homozygous deletion) GSTM1 genotype (OR=2.8, 95% CI=0.9–8.4). The odds ratio for the interactive term (CYP1A1*2A by GSTM1) in logistic regression was 2.7 (95% CI=0.5–15.3). An association between lung cancer and the homozygous CYP1A1*2A genotype is confirmed. An apparent and biologically plausible interaction is suggested between this genotype and GSTM1.     

Association of the UCP polymorphisms with susceptibility to obesity: case–control study and meta-analysis

This paper describes a case–control study and a meta-analysis performed to evaluate if the following polymorphisms are associated with presence of obesity: ?3826A/G (UCP1); ?866G/A, Ala55Val and Ins/Del (UCP2) and ?55C/T (UCP3). The case–control study enrolled 282 obese and 483 non-obese patients with type 2 diabetes. A literature search was made to identify all studies that evaluated associations between UCP1–3 polymorphisms and obesity. In the case–control study the distributions of the UCP variants did not differ between obese and non-obese groups (P > 0.05). Forty-seven studies were eligible for the meta-analysis and the results showed that the UCP2 ?866G/A and UCP3 ?55C/T polymorphisms were associated with protection to obesity in Europeans (OR = 0.89, 95 % CI 0.82–0.97 and OR = 0.88, 95 % CI 0.80–0.97, respectively). The UCP2 Ala55 val polymorphism was associated with obesity in Asians (OR = 1.61, 95 % CI 1.13–2.30). The UCP2 Ins/Del polymorphism was associated with obesity mainly in Europeans (OR = 1.19, 95 % CI 1.00–1.42). There was no significant association of the UCP1 ?3826A/G polymorphism with obesity. In our case–control study we were not able to demonstrate any association between UCP polymorphisms and obesity in T2DM patients; however, in the meta-analysis we detected a significant association of UCP2 ?866G/A, Ins/Del, Ala55Val and UCP3 ?55C/T polymorphisms with obesity.