Distribution of GSTM1, GSTT1, GSTP1 and TP53 disease-associated gene variants in native and urban Venezuelan populations

The contemporary Venezuelan population is the product of major admixture process across various historical events, which has provided it a particular genetic background. The aim of this study concerns the analysis of glutathione S-transferase (GST) GSTM1, GSTP1 and GSTT1 genetic variants and five polymorphisms at the TP53 gene, which are related to cancer susceptibility, in an urban/admixed population and five Amerindian tribes (Bari, Panare, Pemon, Warao and Wayuu) from Venezuela. Genotyping was carried out in 120 individuals from an urban sample and 188 Amerindians. The analysis performed on TP53 haplotype and GST allele distribution showed a close correlation for Pemon and Warao populations, while Bari group appears isolated from the other populations. GSTT1 null variant frequency in our admixed (11%) and native samples (0.0–11.4%) was lower when compared with Caucasians, Africans and Asians. Frequency of the GSTP1*Val cancer-associated allele found in Bari (88.6%) and Panare (63.0%) is of the highest so far reported. Fourteen TP53 haplotypes were observed in the admixed populations, whereas only 3 to 5 in Amerindians. To our knowledge this is the first report of GST polymorphisms and TP53 haplotype distribution in Venezuelans. The distribution of most of analyzed polymorphisms in the urban sample is consistent with the admixed origin of the present-day population of Venezuela. While, the inter-ethnic variations in genetic polymorphisms found in Native American tribes seem to be the result of the influence of demographic factors. These results provide additional data for undertaking ethnographic and disease association studies in Venezuela.     

Secretoglobin 1A member 1 (SCGB1A1) + 38A/G polymorphism is associated with asthma risk: A meta-analysis

Background

Epidemiological studies have evaluated the association between Secretoglobin 1A member 1 (SCGB1A1) + 38A/G polymorphism and asthma, but the results remain inconclusive. The aim of this study was to perform a meta-analysis to investigate a more authentic association between SCGB1A1 + 38A/G polymorphism and asthma.

Methods

Published literature from PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Embase databases were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random or fixed-effect model according the between-study heterogeneity.

Results

A total of 19 case-control studies in 18 articles were included in the meta-analysis, including 3191 cases and 5182 controls. We found that SCGB1A1 + 38A/G polymorphism was associated with a significantly increased risk of asthma risk when all studies were pooled in a dominant model (OR = 1.29; 95% CI 1.08–1.54; P = 0.005). The cumulative meta-analysis and sensitivity analysis further strengthened the stability of the result. Furthermore, publication bias was not detected.

Conclusions

This study suggested that SCGB1A1 + 38A/G polymorphism was a risk factor for asthma. Further large and well-designed studies are needed to confirm this association.     

Association of glutathione S-transferase polymorphisms (GSTM1 and GSTT1) with primary open-angle glaucoma: An evidence-based meta-analysis

Studies investigating the associations between glutathione S-transferase (GST) genetic polymorphisms and primary open-angle glaucoma (POAG) have reported controversial results. Therefore, a meta-analysis was performed to clarify the effects of GSTM1 and GSTT1 polymorphisms on POAG risk. Published literatures from PubMed, EMBASE, ISI Web of Science and CBM databases were retrieved. All studies evaluating the association between GSTM1/GSTT1 polymorphisms and POAG were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effects model. Eleven studies on GSTM1 (1339 cases and 1412 controls) and seven studies on GSTT1 (958 cases, 1003 controls) were included. Overall analysis showed that the association between GSTM1 and GSTT1 null genotype and POAG risk is not statistically significant. Subgroup analyses showed that the null genotype of GSTM1 increased the risk of POAG in Asians. In GSTM1–GSTT1 interaction analysis, individuals with dual null genotype were associated with a significantly increased risk of POAG when compared with the dual present genotype. In conclusion, the present meta-analysis suggested that GSTM1 null genotypes are associated with increased POAG risk in Asian populations but not in Caucasian and mixed populations. Dual null genotype of GSTM1/GSTT1 is associated with increased risk of POAG. Given the limited sample size, the finding on GST polymorphisms needs further investigation.     

GSTM1, GSTT1, GSTP1, and GSTA1 genetic variants are not associated with coronary artery disease in Taiwan

Background and objective

The genetic variants of xenobiotic-metabolizing enzymes, such as those encoded by glutathione-S-transferase (GST) genes, may be associated with the risk of coronary artery disease (CAD). To investigate the genetic factors for CAD, we examined the GSTM1, GSTT1, GSTP1, and GSTA1 genotypes in a CAD cohort in Taiwan.

Methods

Our study included 458 CAD participants and 209 control participants who received coronary angiography to assess CAD. The severity of CAD was defined as the number of coronary vessels with 50% or greater stenosis. Sequence variation of the GSTM1 and GSTT1 genes was determined using a polymerase chain reaction (PCR). The GSTP1 (Ile105Val), and GSTA1 (-69C > T) genetic variants were identified using a combination of PCR and restriction fragment length polymorphism analysis. Logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals.

Results

Among the GST genetic variants examined, the GSTT1 null genotype was more prevalent in CAD participants with 3 stenosed vessels than in control participants (OR = 1.64, P = .02). This association was no longer observed after adjusting for age, sex, smoking, alcohol use, diabetes mellitus, and serum levels of total cholesterol and high-density lipoprotein cholesterol (OR = 1.28, P = .40). Both univariate and multivariate logistic regression analyses found no significant associations between CAD and the other genetic variants, either separately or in combination. In addition, no effects of interactions between the genotypes and environmental factors, such as cigarette smoking, were significantly associated with the risk of CAD.

Conclusion

The GST genetic variants examined were not associated with susceptibility to CAD in our Taiwanese cohort. This null association requires further confirmation with larger samples.     

Effects of passive smoking on breast cancer risk in pre/post-menopausal women as modified by polymorphisms of PARP1 and ESR1

Objectives

The association between passive smoking and breast cancer risk differs in pre- and post-menopausal women. We aimed to explore the modification effects of PARP1 rs1136410 and ESR1 rs2234693 on the association between passive smoking and breast cancer risk among pre- and post-menopausal women.

Design and methods

A case–control study of 839 breast cancer cases and 863 controls was conducted. The gene–environment interactions were tested after adjusting for potential breast cancer risk factors with unconditional logistic regression models.

Results

We found that the effect of passive smoking was modified by the genotypes in both pre- and post-menopausal women, but in opposite directions. The combination of the TC/CC genotypes of ESR1 rs2234693 and passive smoking significantly increased the risk of breast cancer [OR (95%CI): 2.06 (1.39–3.05)] in pre-menopausal women. A significant association was observed between TT genotype and passive smoking [OR (95%CI): 2.40 (1.27–4.53)] in postmenopausal women. For PARP1 rs1136410, similar differential associations were observed, but the interactions were not significant.

Conclusions

These results imply that the risk of breast cancer from passive smoking may be influenced by genetic factors, and that the association may differ depending on menopausal status.     

Combined effects of the UGT1A1 and OATP2 gene polymorphisms as major risk factor for unconjugated hyperbilirubinemia in Indian neonates

Genetic association studies have linked a number of single nucleotide polymorphisms (SNPs) with unconjugated hyperbilirubinemia. The present study was undertaken to validate the association of SNPs with development of hyperbilirubinemia in Indian neonates. Genotyping of five SNPs in two candidate genes was performed in 126 infants with hyperbilirubinemia and 181 controls by PCR-RFLP, Gene Scan analysis and direct DNA sequencing. Genetic polymorphisms of the UGT1A1 promoter, specifically the − 3279 T ? G phenobarbital responsive enhancer module (rs4124874) and (TA)7 dinucleotide repeat (rs8175347) as well as the coding region variants (rs2306283 and rs4149056) of the OATP2 gene were significantly higher among the cases than the controls. The presence of the mutant haplotypes either in homozygous, heterozygous or compound heterozygous state had a significant effect on neonatal hyperbilirubinemia as well as on the requirement of phototherapy than those with the wild haplotype. Further, a significantly higher number of hyperbilirubinemic cases had ≥ 3 variants than the controls (73.80% vs 40.36%, p < 0.0001) and the mean total serum bilirubin levels and requirement of phototherapy also increased according to the number of variants co-expressed. This study demonstrates that UGT1A1 and OATP2 polymorphisms were associated with altered bilirubin metabolism and could be genetic risk factors for neonatal hyperbilirubinemia.     

Association of POL1, MALT1, MC4R, PHLPP and DSEL single nucleotide polymorphisms in chromosome 18q region with type 2 diabetes in Tunisians

Previous studies and replication analyses have linked chromosome 18q21.1–23 with type 2 diabetes (T2DM) and its complications, including diabetic nephropathy (DN). Here we investigated the association of POL1-nearby variant rs488846, MALT1-nearby variant rs2874116, MC4R-nearby variant rs1942872, PHLPP rs9958800 and DSEL-nearby variant rs9966483 single nucleotide polymorphisms (SNPs) in the 18q region, previously linked with DN in African-Americans, with T2DM in (North African) Tunisian subjects, followed by their association with DN, which was performed subsequent to the analysis of the association with T2DM. Study subjects comprised 900 T2DM cases and 748 normoglycemic control, and genotyping was carried out by PCR–RFLP analysis. Of the 5 SNPs analyzed, POL1-nearby variant rs488846 [P = 0.044], and MC4R-nearby variant rs1942872 [P = 0.012] were associated with moderate risk of T2DM. However, there was a lack of consistency in the association of the 5 tested SNPs with DN. As such, it appears that the three chromosome 18q region variants appear to play a role in T2DM pathogenesis, but not with DN in North African Tunisian Arabs.     

Association between MDR1 C3435T polymorphism and risk of breast cancer

The C3435T (rs1045642) polymorphism, located in multi-drug resistance gene 1 (MDR1), has demonstrated its role in decreasing the P-gp activity level which is related to the carcinogenesis. Many published studies have evaluated the association between the MDR1 C3435T polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of the association between MDR1 C3435T polymorphism and risk of breast cancer, we performed a meta-analysis comprised of 10 case–control studies, including 5282 breast cancer cases and 7703 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. The overall results indicated that the variant genotypes were associated with a significantly increased risk of breast cancer (TT versus CC: OR = 1.45, 95% CI = 1.14–1.30, TT versus CT/CC: OR = 1.13, 95% CI = 1.04–1.23, TT/CT versus CC: OR = 1.22, 95% CI = 1.02–1.46). Our results suggest that the MDR1 C3435T polymorphism may contribute to individual susceptibility to breast cancer.     

GSTP1 Ile105Val polymorphism and colorectal cancer risk: An updated analysis

Background

Many studies have investigated the association between the Glutathione S transferase-P1 (GSTP1) Ile105Val polymorphism and colorectal cancer (CRC) susceptibility, but the results were conflicting. The aim of this study is to quantitatively summarize the relationship between this polymorphism and CRC risk.

Methods

Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure (CNKI) and Chinese Biomedicine databases for studies published before December 2012. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for GSTP1 polymorphism and CRC were calculated in a fixed-effects model (the Mantel–Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate.

Results

This meta-analysis included 29 case–control studies, which included 8160 CRC cases and 10,450 controls. Overall, the variant genotypes (ValVal and IleVal) of the Ile105Val were not associated with CRC risk when compared with the wild-type IleIle homozygote. Similarly, no associations were found in the dominant and recessive models. When stratifying for ethnicity, source of controls, study sample size and genotyping methods, no evidence of significant association was observed in any subgroup, except among those studies taking others as genotyping methods (recessive model, OR = 0.71, 95%CI = 0.52–0.96). Limiting the analysis to the studies within Hardy–Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study.

Conclusion

This updated meta-analysis suggests that the GSTP1 Ile105Val polymorphism may not be associated with CRC risk, while the observed decrease in risk of CRC may be due to small-study bias.     

Association between the IRS1 and FTO genes regulates body weight in rabbits

Insulin receptor substrate (IRS) proteins play key roles in signal transduction in insulin and insulin-like growth factor signaling to control postnatal growth. The fat mass and obesity-associated (FTO) protein also play an essential role in postnatal growth. The aim of this study was to investigate the association between the IRS1 and FTO genes and the regulation of growth traits in rabbits. A total of nine synonymous SNPs were detected in the IRS1 coding sequence using direct sequencing, and the c.189G>T and c.2574G>A SNPs from two linkage disequilibrium blocks were further genotyped for association analysis in 216 New Zealand rabbits. The association results revealed that the TT genotype of c.189G>T and the AA genotype of c.2574G>A were significantly associated with higher body weight at 70 (BW70) and 84 (BW84) days of age and with higher average daily gain (P < 0.05). Linear-regression analysis revealed that the two-gene combination model of FTO c.499G>A and IRS1 c.2574G>A was associated with BW70 and BW84. The combination model of the GA genotype of FTO c.499G>A with the AA genotype of IRS1 c.2574G>A was associated with preferred values for BW70 and BW84. The performance values for the FTO c.499G>A genotypes after stratification with regard to the IRS1 c.189G>T genotypes revealed that the TT genotype of IRS1 c.189G>T reduced the FTO c.499G>A significance associated with BW70 and BW84. Together, our data indicated that the IRS1 gene was associated with growth traits in rabbits. The IRS1 and FTO combination model may be exploited to assist breeders in selecting rabbits with preferred body weight.     

Mutational screening of SF1 and WNT4 in Tunisian women with premature ovarian failure

Background

WNT4 and SF1 genes play an important role in ovarian development. They constitute coherent candidate genes associated with premature ovarian failure (POF) pathogenesis.

Methods

We sequenced the coding region of WNT4 and SF1 in 55 Tunisian women with POF and 100 healthy controls.

Results

We identified a synonymous variation in WNT4 (c.99G>A, p.Ser33Ser) and a substitution (c.G437C) in SF1 gene inducing G146 to Ala (GGG–GCG) missense mutation. WNT4 (c.99G>A, p.Ser33Ser) was not associated with POF pathology. However, a positive association of SF1 Gly146Ala polymorphism was noted. Gly146Ala minor allele frequency was significantly higher (p = 0.029) in POF patients versus controls and Ala allele containing genotypes (p = 0.005) were positively associated with POF pathology. The carriage of 146Ala allele was also associated with a significant reduction in estradiol plasma levels.

Conclusions

SF1 Gly146Ala polymorphism seems to be associated with POF pathology in the Tunisian population likely by reducing estradiol levels.     

Intestinal tube formation in Caenorhabditis elegans requires vang-1 and egl-15 signaling

Understanding how epithelial organs form during morphogenesis is a major problem in developmental biology. In the present paper, we provide a detailed analysis of vang-1, the only homolog of the planar cell polarity protein Strabismus/Van Gogh in Caenorhabditis elegans. We demonstrate that during organogenesis of the intestine, (i) VANG-1 specifically interacts with PDZ 2 domain of DLG-1 (Discs large) and becomes phosphorylated by the kinase domain of the FGF-like receptor tyrosine kinase EGL-15; (ii) VANG-1 is predominantly restrained to the cell cortex but relocates to the apical junction; and (iii) in vang-1 embryos epithelial cells of the intestine are not correctly arranged along the anterior-posterior axis. To investigate what determines the disposition of the VANG-1 protein, either truncated protein forms were expressed in the intestine or RNAi was used to remove the functions of gene products previously shown to be involved in apical junction formation. Removal of the VANG-1 PDZ binding motif “− ESAV” and depletion of dlg-1 or let-413 gene functions interferes with the localization of VANG-1. In addition, egl-15 embryos show a premature relocation of VANG-1 to the apical junction, causing defects that resemble those observed in mutant vang-1 embryos and after intestine-specific overexpression of full-length vang-1. Finally, the localization of VANG-1 depends on DSH-2, a homolog of the planar cell polarity protein Dishevelled and depletion phenocopies vang-1 and egl-15 phenotypes in the embryonic intestine.     

Mutation and expression analysis of the IDH1, IDH2, DNMT3A, and MYD88 genes in colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of death around the world. Its genetic mechanism was intensively investigated in the past decades with findings of a number of canonical oncogenes and tumor-suppressor genes such as APC, KRAS, and TP53. Recent genome-wide association and sequencing studies have identified a series of promising oncogenes including IDH1, IDH2, DNMT3A, and MYD88 in hematologic malignancies. However, whether these genes are involved in CRC remains unknown. In this study, we screened the hotspot mutations of these four genes in 305 CRC samples from Han Chinese by direct sequencing. mRNA expression levels of these genes were quantified by quantitative real-time PCR (RT-qPCR) in paired cancerous and paracancerous tissues. Association analyses between mRNA expression levels and different cancerous stages were performed. Except for one patient harboring IDH1 mutation p.I99M, we identified no previously reported hotspot mutations in colorectal cancer tissues. mRNA expression levels of IDH1, DNMT3A, and MYD88, but not IDH2, were significantly decreased in the cancerous tissues comparing with the paired paracancerous normal tissues. Taken together, the hotspot mutations of IDH1, IDH2, DNMT3A, and MYD88 gene were absent in CRC. Aberrant mRNA expression of IDH1, DNMT3A, and MYD88 gene might be actively involved in the development of CRC.     

GSTM1 and GSTT1 gene polymorphisms as major risk factors for bronchopulmonary dysplasia in a Chinese Han population

Bronchopulmonary dysphasia (BPD) is a complex multifactorial disease with an obvious genetic predisposition. Oxidative stress plays an important role in its pathogenesis. Glutathione S-transferases (GSTs) detoxify metabolites produced by oxidative stress within the cell and protect the cells against injury. In the present study, the hypothesis that polymorphisms in the GSTM1 and GSTT1 genes are associated with BPD in Chinese Han infants was examined. Sixty infants with BPD and 100 gestational age and birth weight-matched preterm infants without BPD were recruited. Genotyping for GSTM1 and GSTT1 was performed by multiplex polymerase chain reaction (PCR). The GSTM1 null genotype was more prevalent in BPD infants (65.0%) than in the control subjects (48.0%), which yielded higher risk towards BPD (odds ratio (OR): 2.012, 95% confidence interval (CI) = 1.040–3.892, p = 0.037). There was no statistically significant association of GSTT1 genotype with BPD (OR: 1.691, 95% CI = 0.884–3.236, p = 0.111), although the frequency of GSTT1 null genotype was higher among the BPD subjects (60.0%) than in the control patients (47.0%). GSTM1 and GSTT1 double null genotype was also higher in BPD group (38.3%) than in controls (21.0%) with a higher risk towards BPD (OR: 2.338, 95%CI = 1.151–4.751, p = 0.017). The results suggest that null genotypes of GSTM1 and GSTT1 genes may contribute to the development of BPD in our Chinese Han population.     

Association of BANK1 and cytokine gene polymorphisms with type 1 diabetes in Tunisia

Type 1 diabetes (T1D) is an autoimmune disease (AID) with both genetic and environmental components. We aimed to investigate the genetic association of polymorphisms in genes previously linked with other AIDs, namely BANK1, IL15 and IL2/IL21 region.     

Null genotypes of GSTM1 and GSTT1 contribute to increased risk of diabetes mellitus: A meta-analysis

Diabetes mellitus (DM) is a common disease which results from various causes including genetic and environmental factors. Glutathione S-Transferase M1 (GSTM1) and Glutathione S-Transferase T1 (GSTT1) genes are polymorphic in human and the null genotypes lead to the absence of enzyme function. Many studies assessed the associations between GSTM1/GSTT1 null genotypes and DM risk but reported conflicting results. In order to get a more precise estimate of the associations of GSTM1/GSTT1 null genotypes with DM risk, we performed this meta-analysis. Published literature from PubMed, Embase and China Biology Medicine (CBM) databases was searched for eligible studies. Pooled odds ratios (OR) and corresponding 95% confidence intervals (95%CI) were calculated using a fixed- or random-effects model. 11 publications (a total of 2577 cases and 4572 controls) were finally included into this meta-analysis. Meta-analyses indicated that null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1–GSTT1 were all associated with increased risk of DM (GSTM1: OR _{random-effects} = 1.60, 95%CI 1.10–2.34, P_OR = 0.014; GSTT1: OR _{random-effects} = 1.47, 95%CI 1.12–1.92, P_OR = 0.005; GSTM1–GSTT1: OR _{fixed-effects} = 1.83, 95%CI 1.30–2.59, P_OR = 0.001). Subgroup by ethnicity suggested significant associations between null genotypes of GSTM1 and GSTT1 and DM risk among Asians (GSTM1: OR _{random-effects} = 1.77, 95%CI 1.24–2.53, P_OR = 0.002; GSTT1: OR _{random-effects} = 1.58, 95%CI 1.09–2.27, P_OR = 0.015). This meta-analysis suggests null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1–GSTT1 are all associated with increased risk of DM, and null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1–GSTT1 are potential biomarkers of DM.     

Impacts and interactions of PDGFRB, MMP-3, TIMP-2, and RNF213 polymorphisms on the risk of Moyamoya disease in Han Chinese human subjects

Polymorphisms of PDGFRB, MMP-3, TIMP-2, RNF213, TGFB1, Raptor and eNOS genes have been associated with Moyamoya disease (MMD) separately in studies, but their interactions on MMD have never been evaluated in one study. This study enrolled 96 MMD patients and 96 controls to evaluate the contributions and interactions of these polymorphisms on MMD in Chinese Hans. After genotyping, five polymorphisms loci were deemed suitable for analysis, rs3828610 in PDGFRB, rs3025058 in MMP-3, rs8179090 in TIMP-2, rs112735431 and rs148731719 in RNF213. Interactions of different loci on MMD were evaluated by multifactor dimensionality reduction (MDR) method. Significantly higher frequencies of A allele and G/A genotype of rs112735431 in RNF213 were observed in MMD patients compared with controls (P = 0.011; P = 0.018, respectively). In the dominant model, G/A genotype of rs112735431 was associated with increased risk of MMD (P = 0.018). A higher frequency of G allele and G/G genotype of rs148731719 in RNF213 gene in patient than control group (P < 0.001; P < 0.01, respectively) was also detected. No significant association between MMD and other three loci (P > 0.05) was detected. MDR analysis failed to detect any significant interaction among these five loci in the occurrence of MMD (P > 0.05), but the combination of three loci (rs112735431 in RNF213, rs3828610 in PDGFRB, rs3025058 in MMP-3) could have the maximum testing accuracy (57.29%) and cross-validation consistency (10/10). The results indicated that RNF213 rs112735431 and rs148731719 may exert a significant influence on MMD occurrence. Compared with this overwhelming effect, the influences of PDGFRB, MMP-3, and TIMP-2 on MMD may be unremarkable in Chinese Hans. There may be no prominent interaction among these five gene polymorphisms on the occurrence of MMD.     

Lack of association between genetic polymorphisms in ROBO1, MRPL19/C2ORF3 and THEM2 with Developmental Dyslexia

Developmental Dyslexia (DD) is a heritable, complex genetic disorder characterized by specific impairment in reading and writing ability that is substantially below the expected reading ability given the person's chronological age, measured intelligence and age-appropriate education. More than ten susceptible genes have been identified for DD. A Single Nucleotide Polymorphism (SNP) of these genes was found to be associated with various phenotypes of DD. To identify the role of SNPs of four candidate genes namely, MRPL19/C2ORF3, ROBO1 and THEM2 in an Indian population, we genotyped eight SNPs of these genes in 157 children with DD and 212 normal readers using a MassARRAY technique with a MALDI-TOF MS analyzer. Power analysis of some of these SNPs showed > 80% of power. Chi-square test, Odds Ratios (ORs), 95% Confidence Intervals (CIs) and Bonferroni's correction were applied to identify the significance of the genotyped SNPs and haplotypes. Our study failed to show any association of SNPs and haplotypes of these genes with DD in an Indian population.     

Impact of genetic variants of IL-6, IL6R, LRP5, ESR1 and SP7 genes on bone mineral density in postmenopausal Mexican-Mestizo women with obesity

Background

Since obesity and osteoporosis present a high genetic predisposition and polymorphisms of IL-6, IL6R, LRP5, ESR1 and SP7 may influence the risk of both diseases, the aim of this study was to analyze the possible association of polymorphisms in these genes, as well as their haplotypes, with BMD variations in postmenopausal Mexican-Mestizo women with grade 2 or grade 3 obesity.

Methods

One hundred eighty unrelated postmenopausal women with grade 2 or grade 3 obesity were included. BMD was measured in total hip and lumbar spine by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. Rs1800795 of IL-6, rs2228145 of IL6R, rs3736228 of LRP5, rs9340799 (XbaI) and rs2234693 (PvuII), of ESR1, rs10876432 and rs2016266, of SP7 (and their haplotypes), were studied by real-time PCR allelic discrimination. Deviations from Hardy–Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r², and haplotype analysis was conducted.

Results

Using WHO criteria, 54.5% had grade 2 obesity, and 45.5% had grade 3 obesity. Regarding DXA results, 11.1% women had osteoporosis, 41.7% had osteopenia, and 47.2% had normal BMD. Genotype and haplotype analysis showed no significant differences with BMD variations at the lumbar spine, total hip or femoral neck.

Conclusions

We did not find a significant association between the polymorphisms analyzed or their haplotypes and BMD variations in postmenopausal women with obesity. The higher BMD observed in women with obesity could be the result of an adaptive response to the higher loading of the skeleton.     

Relationship between CCR2-V64I polymorphism and cancer risk: A meta-analysis

Background and objectives

The role of CCR2-V64I polymorphism in various cancers has been reported in many studies. However, results from published studies on the association between CCR2-V64I polymorphism and cancer risk are conflicting. Therefore, we performed a meta-analysis to estimate the overall cancer risk associated with the polymorphism.

Methods

Electronic searches of PubMed and EMBASE were conducted for all publications on the association between this variant and cancer. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association.

Results

Sixteen studies with 2661 cancer patients and 5801 healthy controls were included. Overall, significant association was found between the CCR2-V64I polymorphism and cancer risk (OR = 1.84, 95% CI = 1.35–2.51, AA vs GA/GG, P = 0.37). In the subgroup analysis stratified by cancer types, there was a significant association between this polymorphism and bladder cancer (OR = 2.06, 95% CI = 1.02–4.15, AA vs GA/GG, P = 0.11), cervical cancer (OR = 3.34, 95% CI = 1.48–7.50, AA vs GG, P = 0.56), and oral cancer (OR = 2.04, 95% CI = 1.46–2.84, GA vs GG, P = 0.70). In the subgroup analysis stratified by ethnicities, an increased cancer risk was also found in Europeans (OR = 2.31, 95% CI = 1.45–3.68, AA vs GA/GG, P = 0.16) and Asians (OR = 1.88, 95% CI = 1.12–3.16, AA vs GA/GG, P = 0.92).

Conclusion

This meta-analysis suggested that CCR2-V64I polymorphism may contribute to an increased risk of cancer.