Evaluation Of Single Nucleotide Polymorphisms Research Articles

D23 - Pharmacogenomic evaluation of single nucleotide polymorphisms associated with oxaliplatin-induced peripheral neuropathy: a preliminary study

D23 - Pharmacogenomic evaluation of single nucleotide polymorphisms associated with oxaliplatin-induced peripheral neuropathy: a preliminary study

Cervical Cancer Genetic Susceptibility: A Systematic Review and Meta-Analyses of Recent Evidence.

IntroductionCervical cancer (CC) has one of the highest mortality rates among women worldwide. Several efforts have been made to identify the genetic susceptibility factors underlying CC development. However, only a few polymorphisms have shown consistency among studies.Materials and MethodsWe conducted a systematic review of all recent case-control studies focused on the evaluation of single nucleotide polymorphisms (SNPs) and CC risk, stringently following the “PRISMA” statement recommendations. The MEDLINE data base was used for the search. A total of 100 case-control studies were included in the meta-analysis. Polymorphisms that had more than two reports were meta-analyzed by fixed or random models according to the heterogeneity presented among studies.ResultsWe found significant negative association between the dominant inheritance model of p21 rs1801270 polymorphism (C/A+A/A) and CC (pooled OR = 0.76; 95%CI: 0.63–0.91; p<0.01). We also found a negative association with the rs2048718 BRIP1 polymorphism dominant inheritance model (T/C+C/C) and CC (pooled OR = 0.83; 95%CI: 0.70–0.98; p = 0.03), as well as with the rs11079454 BRIP1 polymorphism recessive inheritance model and CC (pooled OR = 0.79; 95%CI: 0.63–0.99; p = 0.04). Interestingly, we observed a strong tendency of the meta-analyzed studies to be of Asiatic origin (67%). We also found a significant low representation of African populations (4%).ConclusionsOur results provide evidence of the negative association of p21 rs1801270 polymorphism, as well as BRIP1 rs2048718 and rs11079454 polymorphisms, with CC risk. This study suggests the urgent need for more replication studies focused on GWAS identified CC susceptibility variants, in order to reveal the most informative genetic susceptibility markers for CC across different populations.

Abstract P5-08-24: Evaluation of single nucleotide polymorphisms (SNPs) as predictive factors of progression (PFS) and metastatic (MFS) free survival in adjuvant breast cancer (BC)

Abstract Background: Adjuvant chemotherapy (ACT) using anthracyclines and taxanes is a standard treatment for BC. Usual criteria as age, SBR grade, HER2 or hormonal status (HS), estrogen receptor (ER), triple negative BC, histological type, lymphovascular invasion (LVI), Ki67, tumor size and lymph node involvement are not yet sufficient for ACT decision. As SNPs located in genes involved in metabolism or transport of cytotoxic drugs may affect efficacy of ACT, we investigated the potential of 49 SNPs to predict response to ACT in BC. Methods: From 01/2008 to 01/2012, 418 patients (pts) with BC treated with ACT were included. 309 pts received FEC100-Docetaxel regimen (cohort 1), and 109 pts with HER2 overexpression FEC100-Docetaxel-Trastuzumab regimen (cohort 2). Genotyping of 49 SNPs was performed on germline DNA using real time PCR with SNPType (Fluidigm) or Taqman probes (Life technologies) on BioMark Platform (Fluidigm). PFS, MFS and overall survival (OS) were estimated by Kaplan-Meier method. Association of clinicopathologic features (CPF) with PFS/MFS was evaluated by log-Rank test. After ensuring Hardy-Weinberg equilibrium was respected, PFS/MFS were correlated to CPF and genotypes, using univariate and multivariate Cox logistic regression. A prognostic score was established. Results: PFS, MFS and OS rates were respectively 81.8%, 83.4% and 87.3% in cohort 1 (3.4 years of median follow up (FU)) and 90.1%, 90% and 93.8% in cohort 2 (4 years of FU). In cohort 1, univariate analysis revealed that 5 SNPs, SLCO1B3 (rs11045585), NOS3 (rs1799983), CYB2B6 (rs2279345), BRCA1 (rs799917) and CYP2D6 (rs3892097) were associated with MFS. Genotypes, HR, 95%CI and p value are as follows: SLCO1B3 GG 7.73 (1.83-32.7) p=0.001, NOS3 GT 0.32 (0.14-0.76) p=0.006, CYB2B6 TT 2.29 (1.02-5.13) p=0.04, BRCA1 CT 0.41 (0.19-0.89) p=0.02, and CYP2D6 AG 2.14 (1.05-4.36) p=0.03. Multivariate analysis revealed that 4 SNPs remained associated with metastatic risk: CYB2B6; TT 2.38 (1.05-5.41) p=0.038, NOS3; GG-TT 3.11 (1.33-7.27) p=0.009, BRCA1; CC-TT 2.21 (1.01-4.85) p=0.047, CYP2D6; AG 2.14(1.04-4.40) p=0.039. No CPF was associated with survival. Prognostic model revealed a metastatic risk of 10.25 (1.29-81.31) if these four adverse genotypes coexist. In cohort 2, subject to limited number of events, age (p=0.03), HS (p=0.06), ER (p=0.05), LVI (p=0.02) tumor size (p=0.003) and 2 SNPs were associated in univariate with PFS: CYB2B6 (rs2279345); CT 5.73 (1.22-27) p=0.01, MTHFR (rs1801133); CT 4.61 (0.98-21.7) p=0.03. Multivariate analysis showed unfavorable PFS for heterozygous patients for CYB2B6 or for MTHFR: 9.67 (1.82-51.28) p=0.008 and 5.62(1.19-26.59) p=0.03 respectively and if tumor size was ≥T2 10.78 (2.12-54.90) p=0.004. Conclusion: SNPs of genes involved in oxidative stress (NOS3 rs1799983; GG-TT), docetaxel transport (SLCO1B3 rs11045585; GG) cyclophosphamide (CYB2B6 rs2279345; TT in cohort 1 ou CT in cohort 2) and 5FU metabolism (MTHFR rs1801133; CT), or DNA repair (BRCA1rs799917; CC-TT) are associated with survival in pts treated with ACT. BRCA1, CYB2B6 and SLCO1B3 represent potential attractive tools for guiding ACT indication. Citation Format: Ducoulombier A, Dumont A, Revillion F, Bonneterre J, Peyrat J-P. Evaluation of single nucleotide polymorphisms (SNPs) as predictive factors of progression (PFS) and metastatic (MFS) free survival in adjuvant breast cancer (BC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-24.

The role of adipokines in ischemic stroke risk stratification.

Adiponectin, leptin, and resistin are the most well-studied adipokines and play important roles in the regulation of glucose metabolism, subclinical inflammation, and cardiovascular homeostasis. Accordingly, measurement of adipokine levels might be useful in cardiovascular risk stratification. Moreover, the study of single-nucleotide polymorphisms of genes that encode these adipokines might also represent a valuable predictive tool in cardiovascular disease prevention strategies. To summarize the biologic role of the adipokines adiponectin, leptin, and resistin and the prognostic value of their serum levels regarding the occurrence and outcome of ischemic stroke. We also discuss the relationship of single-nucleotide polymorphisms of the adiponectin, leptin genes, and the -420C > G polymorphism of resistin gene with stroke risk. Several studies in the general population evaluated the association between these adipokines and stroke risk, yielding conflicting results. There are more limited data regarding the effect of these adipokines on stroke severity and outcome. A small number of studies also assessed the predictive role of single-nucleotide polymorphisms of the adiponectin, leptin, and resistin genes regarding stroke risk, but the findings were also controversial. It is unclear whether adiponectin, leptin, and resistin levels or the single-nucleotide polymorphisms of their encoding genes are independently associated with stroke risk. However, given the role of these adipokines in the pathogenesis of atherosclerosis, larger prospective studies, both in the general population and in patients with a history of stroke, are needed to determine whether the measurement of serum levels of these adipokines or the evaluation of single-nucleotide polymorphisms in their encoding genes could improve stroke risk prediction. If this relationship is proven, therapeutic interventions targeting adipokine levels might represent a novel approach to reduce stroke-related mortality and disability.

Identification and Evaluation of Single-Nucleotide Polymorphisms in Allotetraploid Peanut (Arachis hypogaea L.) Based on Amplicon Sequencing Combined with High Resolution Melting (HRM) Analysis.

The cultivated peanut (Arachis hypogaea L.) is an allotetraploid (AABB) species derived from the A-genome (Arachis duranensis) and B-genome (Arachis ipaensis) progenitors. Presence of two versions of a DNA sequence based on the two progenitor genomes poses a serious technical and analytical problem during single nucleotide polymorphism (SNP) marker identification and analysis. In this context, we have analyzed 200 amplicons derived from expressed sequence tags (ESTs) and genome survey sequences (GSS) to identify SNPs in a panel of genotypes consisting of 12 cultivated peanut varieties and two diploid progenitors representing the ancestral genomes. A total of 18 EST-SNPs and 44 genomic-SNPs were identified in 12 peanut varieties by aligning the sequence of A. hypogaea with diploid progenitors. The average frequency of sequence polymorphism was higher for genomic-SNPs than the EST-SNPs with one genomic-SNP every 1011 bp as compared to one EST-SNP every 2557 bp. In order to estimate the potential and further applicability of these identified SNPs, 96 peanut varieties were genotyped using high resolution melting (HRM) method. Polymorphism information content (PIC) values for EST-SNPs ranged between 0.021 and 0.413 with a mean of 0.172 in the set of peanut varieties, while genomic-SNPs ranged between 0.080 and 0.478 with a mean of 0.249. Total 33 SNPs were used for polymorphism detection among the parents and 10 selected lines from mapping population Y13Zh (Zhenzhuhei × Yueyou13). Of the total 33 SNPs, nine SNPs showed polymorphism in the mapping population Y13Zh, and seven SNPs were successfully mapped into five linkage groups. Our results showed that SNPs can be identified in allotetraploid peanut with high accuracy through amplicon sequencing and HRM assay. The identified SNPs were very informative and can be used for different genetic and breeding applications in peanut.

Evaluation of single nucleotide polymorphisms of pvmdr1 and microsatellite genotype in Plasmodium vivax isolates from Republic of Korea military personnel.

BackgroundChloroquine has been administered to the soldiers of the Republic of Korea as prophylaxis against vivax malaria. Recent increase in the number of chloroquine-resistant parasites has raised concern over the chemoprophylaxis and treatment of vivax malaria.MethodsTo monitor the development of chloroquine-resistant parasites in the Republic of Korea, analyses of single nucleotide polymorphisms (SNPs) of pvmdr1 and microsatellite markers were performed using samples collected from 55 South Korean soldiers infected with Plasmodium vivax.ResultsFour SNPs, F1076L, T529, E1233, and S1358, were identified. Among these, S1358 was detected for the first time in Korea. The microsatellite-based study revealed higher genetic diversity in samples collected in 2012 than in 2011.ConclusionsTaken together, the results indicate that P. vivax with a newly identified SNP of pvmdr1 has been introduced into the Korean P. vivax population. Therefore, continuous monitoring for chloroquine-resistant parasites is required for controlling vivax malaria in the Republic of Korea.

Evaluation of single nucleotide polymorphisms in chromosomal regions impacting pregnancy status in cattle.

Reproductive success is an important component of commercial beef cattle production, and identification of DNA markers with predictive merit for reproductive success would facilitate accurate prediction of mean daughter pregnancy rate, enabling effective selection of bulls to improve female fertility. A previous study identified SNP associated with beef cattle reproductive efficiency based on a genomewide association analysis approach using genotyping multiple-animal pools of DNA to increase the number of animals that could be genotyped with available resources. For the current study, we expand on this previous study by individually genotyping cattle from the pooling study for 89 SNP that were associated with female pregnancy rate. The aims of the study were to confirm the results of the pooling study and, more specifically, identify modes of gene action and DNA variations such as haplotypes that would not be possible with pooled genotyping. Eighty-nine SNP selected from the pooling study were evaluated using the Sequenom MassARRAY system to individually genotype animals from populations evaluated in the pooling study, including both and breeds. From this research, regions on chromosomes 5 (26.3-48.1 Mb; UMD3.1 assembly) and 9 (37,436,575 bp; UMD3.1 assembly), first identified in the previous pooling study, were shown through individual genotyping to harbor genetic variation ( < 0.05 genomewide significance) affecting reproductive efficiency in interspecific crosses ( and ) of cattle. Each of these markers exhibited additive (vs. dominant) gene action. Additionally, a haplotype block harboring an allele of origin with negative effects on reproduction was identified on chromosome 5 in interspecific composite breeds of × composites.

Genetics in Diabetic Retinopathy: Current Concepts and New Insights

There is emerging evidence which indicates the essential role of genetic factors in the development of diabetic retinopathy (DR). In this regard it should be highlighted that genetic factors account for 25-50% of the risk of developing DR. Therefore, the use of genetic analysis to identify those diabetic patients most prone to developing DR might be useful in designing a more individualized treatment. In this regard, there are three main research strategies: candidate gene studies, linkage studies and Genome-Wide Association Studies (GWAS). In the candidate gene approach, several genes encoding proteins closely related to DR development have been analyzed. The linkage studies analyze shared alleles among family members with DR under the assumption that these predispose to a more aggressive development of DR. Finally, Genome-Wide Association Studies (GWAS) are a new tool involving a massive evaluation of single nucleotide polymorphisms (SNP) in large samples. In this review the available information using these three methodologies is critically analyzed. A genetic approach in order to identify new candidates in the pathogenesis of DR would permit us to design more targeted therapeutic strategies in order to decrease this devastating complication of diabetes. Basic researchers, ophthalmologists, diabetologists and geneticists should work together in order to gain new insights into this issue.

Genetics in Diabetic Retinopathy: Current Concepts and New Insights

There is emerging evidence which indicates the essential role of genetic factors in the development of diabetic retinopathy (DR). In this regard it should be highlighted that genetic factors account for 25-50% of the risk of developing DR. Therefore, the use of genetic analysis to identify those diabetic patients most prone to developing DR might be useful in designing a more individualized treatment. In this regard, there are three main research strategies: candidate gene studies, linkage studies and Genome-Wide Association Studies (GWAS). In the candidate gene approach, several genes encoding proteins closely related to DR development have been analyzed. The linkage studies analyze shared alleles among family members with DR under the assumption that these predispose to a more aggressive development of DR. Finally, Genome-Wide Association Studies (GWAS) are a new tool involving a massive evaluation of single nucleotide polymorphisms (SNP) in large samples. In this review the available information using these three methodologies is critically analyzed. A genetic approach in order to identify new candidates in the pathogenesis of DR would permit us to design more targeted therapeutic strategies in order to decrease this devastating complication of diabetes. Basic researchers, ophthalmologists, diabetologists and geneticists should work together in order to gain new insights into this issue.

Evaluation of single nucleotide polymorphisms in the miR-183–96–182 cluster in adulthood attention-deficit and hyperactivity disorder (ADHD) and substance use disorders (SUDs)

Attention deficit-hyperactivity disorder (ADHD) is a neuropsychiatric disorder characterized by inappropriate and impaired levels of hyperactivity, impulsivity and inattention. Around 75% of adults with ADHD show comorbidity with other psychiatric disorders such as disruptive behavior disorders or substance use disorders (SUDs). Recently, there has been growing interest in studying the role of microRNAs (miRNAs) in the susceptibility to complex disorders. Interestingly, converging evidence suggests that single nucleotide polymorphisms (SNPs) within miRNAs or miRNA target sites may modulate the miRNA-mediated regulation of gene expression through the alteration of the miRNA maturation, structure or expression pattern as well as the silencing mechanisms of target genes. Genetic studies and animal models support the involvement of the serotonin receptor (HTR1B) in ADHD. We evaluated the contribution of one SNP in the miR-96 target site at HTR1B and eight tagSNPs within the genomic region containing this miRNA in 695 adults with ADHD (266 and 396 subjects with and without comorbid SUD, respectively), 403 subjects with SUD without life-time diagnosis of ADHD and 485 sex-matched controls from Spain. Single and multiple marker analyses revealed association between two SNPs located at the 3′ region of miR-96 (rs2402959 and rs6965643) and ADHD without SUD. Our results provide preliminary evidence for the contribution of two sequence variants at the miR-183–96–182 cluster to ADHD without comorbid SUD, and emphasize the need to take comorbidities into account in genetic studies to minimize the effect of heterogeneity and to clarify these complex phenotypes.

Evaluation of single nucleotide polymorphism of protamine-1 and -2 genes and sperm protamine deficiency in men undergoing ICSI procedure

Evaluation of single nucleotide polymorphism of protamine-1 and -2 genes and sperm protamine deficiency in men undergoing ICSI procedure

Evaluation of single nucleotide polymorphisms in microRNAs (hsa-miR-196a2 rs11614913 C/T) from Brazilian women with breast cancer

BackgroundEmerging evidence has shown that miRNAs are involved in human carcinogenesis as tumor suppressors or oncogenes. Single nucleotide polymorphisms (SNPs) located in pre-miRNAs may affect the processing and therefore, influence the expression of mature miRNAs. Previous studies generated conflicting results when reporting association between the hsa-miR-196a2 rs11614913 common polymorphism and breast cancer.MethodsThis study evaluated the hsa-miR-196a2 rs11614913 SNP in 388 breast cancer cases and 388 controls in Brazilian women. Polymorphism was determined by real-time PCR; control and experimental groups were compared through statistical analysis using the X2 or Fisher’s exact tests.ResultsThe analysis of the SNPs frequencies showed a significant difference between the groups (BC and CT) in regards to genotype distribution (χ2: p = 0.024); the homozygous variant (CC) was more frequent in the CT than in the BC group (p = 0.009). The presence of the hsa-miR-196a2 rs11614913 C/T polymorphism was not associated with histological grades (p = 0.522), axillary lymph node positive status (p = 0.805), or clinical stage (p = 0.670) among the breast cancer patients.ConclusionsThe results of this study indicated that the CC polymorphic genotype is associated with a decreased risk of BC and the presence of the T allele was significantly associated with an increased risk of BC.

Polymorphisms in the fetal progesterone receptor and a calcium-activated potassium channel isoform are associated with preterm birth in an Argentinian population

To investigate genetic etiologies of preterm birth (PTB) in Argentina through evaluation of single-nucleotide polymorphisms (SNPs) in candidate genes and population genetic admixture. Genotyping was performed in 389 families. Maternal, paternal and fetal effects were studied separately. Mitochondrial DNA (mtDNA) was sequenced in 50 males and 50 females. Y-chromosome anthropological markers were evaluated in 50 males. Fetal association with PTB was found in the progesterone receptor (PGR, rs1942836; P=0.004). Maternal association with PTB was found in small conductance calcium activated potassium channel isoform 3 (KCNN3, rs883319; P=0.01). Gestational age associated with PTB in PGR rs1942836 at 32-36 weeks (P=0.0004). MtDNA sequencing determined 88 individuals had Amerindian consistent haplogroups. Two individuals had Amerindian Y-chromosome consistent haplotypes. This study replicates single locus fetal associations with PTB in PGR, maternal association in KCNN3, and demonstrates possible effects for divergent racial admixture on PTB.

An Evaluation of Single Nucleotide Polymorphisms in the Human Heat Shock Protein 90 kDa Alpha and Beta Isoforms

Single nucleotide polymorphisms (SNPs) in genes coding for proteins that maintain the cytosolic aryl hydrocarbon receptor (AHR) complex may affect individual susceptibility to dioxin-like compound (DLC)-induced toxicity. The cytosolic 90 kDa heat shock proteins (HSP90s) are ubiquitous chaperone proteins that bind to and stabilize numerous client proteins, including non-ligand-bound AHR. The objective of this study was to characterize SNPs in the human cytosolic HSP90 genes (HSP90AA1 and HSP90AB1). DNA sequencing of 101 human samples detected eight and seven unique SNPs at the HSP90AA1 and HSP90AB1 loci, respectively. For HSP90AA1, two non-synonymous (L71M and E554D) and one rare early termination (Q107X) SNP were observed. One SNP (E554D) was a rare novel polymorphism located in the middle substrate binding region. All SNPs detected in the HSP90AB1 gene were synonymous. With the exception of Q107X, in silico analyses predicted all HSP90 SNPs would have very low to medium risk of affecting the regulation of alternative splicing in gene transcription or protein function. Overall, a very limited presence of SNPs with predicted functional consequence in key domains of the human HSP90 proteins was observed in this study.

Evaluation of Single Nucleotide Polymorphisms (SNPs) Genotyped by the Illumina Bovine SNP50K in Cattle Focusing on Hanwoo Breed.

In the present study, we evaluated the informativeness of SNPs genotyped by the Illumina Bovine SNP50K assay in different cattle breeds. To investigate these on a genome-wide scale, we considered 52,678 SNPs spanning the whole autosomal and X chromosomes in cattle. Our study samples consists of six different cattle breeds. Across the breeds approximately 72 and 6% SNPs were found polymorphic and fixed or close to fix in all the breeds, respectively. The variations in the average minor allele frequency (MAF) were significantly different between the breeds studied. The level of average MAF observed in Hanwoo was significantly lower than the other breeds. Hanwoo breed also displayed the lowest number of polymorphic SNPs across all the chromosomes. More importantly, this study indicated that the Bovine SNP50K assay will have reduced power for genome-wide association studies in Hanwoo as compared to other cattle breeds. Overall, the Bovine SNP50K assay described in this study offer a useful genotyping platform for mapping quantitative trait loci (QTLs) in the cattle breeds. The assay data represent a vast and generally untapped resource to assist the investigation of the complex production traits and the development of marker-assisted selection programs.

Evaluation of single nucleotide polymorphisms as internal controls in prenatal diagnosis of fetal blood groups

Ziel: Determination of fetal blood groups in plasma of pregnant women is increasingly utilized as an additional diagnostic method. However, test interpretation can fail, if insufficient amplification of fetal DNA occurs (a negative test result is expected, if the fetus is negative but may also occur if the amplification of the fetal DNA fails). To discriminate fetal and maternal DNA we evaluated the use of 52 SNPs as individual internal positive controls (IPC) in our PCR settings for prenatal blood group typing.

Short communication: Effect of mutation age on genomic predictions

Genomic selection relies on the whole-genome evaluation of single nucleotide polymorphisms (SNP), some of them linked to quantitative trait loci (QTL). Although statistical methodology has been developed for the analysis of genomic data, little is known about the performance of SNP association studies when trying to capture variability from QTL mutations of different ages. Within this context, the influence of mutation age was analyzed under a simulation design, assuming presence or absence of selection on mutant QTL alleles. Focusing on a unique chromosome with a single QTL located in the proximal end, the performance of the genomic selection analyses was evaluated in terms of standardized mean square error (MSE). For all simulation scenarios, MSE was highest for the youngest mutations. The MSE was progressively reduced with mutation age under random mating and soft selection, and reached its maximum performance with the oldest mutations. On the other hand, moderate and strong selection caused a quick reduction of the MSE from youngest mutations to mutations arising in generations 920 to 939, thus resulting in a progressive increase for older mutations. In both cases, very young mutations escaped from genomic selection analyses, releasing a relevant amount of genetic variability that could not be captured and used in genomic selection programs. This demonstrated the need for new analytical approaches to model relevant and recent sources of variation; if captured, these young mutations could substantially contribute to current breeding schemes.

Estrogen and progesterone-related gene variants and colorectal cancer risk in women

BackgroundObservational studies and randomized trials have suggested that estrogens and/or progesterone may lower the risk for colorectal cancer. Inherited variation in the sex-hormone genes may be one mechanism by which sex hormones affect colorectal cancer, although data are limited.MethodWe conducted a comprehensive evaluation of single nucleotide polymorphisms (SNPs) in genes encoding 3 hormone receptors (ESR1, ESR2, PGR) and 5 hormone synthesizers (CYP19A1 and CYP17A1, HSD17B1, HSD17B2, HSD17B4) among 427 women with incident colorectal cancer and 871 matched controls who were Caucasians of European ancestry from 93676 postmenopausal women enrolled in the Women's Health Initiative Observational cohort. A total of 242 haplotype-tagging and functional SNPs in the 8 genes were included for analysis. Unconditional logistic regression with adjustment for age and hysterectomy status was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsWe observed a weak association between the CYP17A1 rs17724534 SNP and colorectal cancer risk (OR per risk allele (A) = 1.39, 95% CI = 1.09-1.78, corrected p-value = 0.07). In addition, a suggestive interaction between rs17724534 and rs10883782 in 2 discrete LD blocks of CYP17A1 was observed in relation to colorectal cancer (empirical p value = 0.04). Moreover, one haplotype block of CYP19A1 was associated with colorectal cancer (corrected global p value = 0.02), which likely reflected the association with the tagging SNP, rs1902584, in the block.ConclusionOur findings offer some support for a suggestive association of CYP17A1 and CYP19A1 variants with colorectal cancer risk.

Evaluation of single nucleotide polymorphisms of Pro12Ala in peroxisome proliferator-activated receptor-&amp;gamma; and Gly308Ala in tumor necrosis factor-&amp;alpha; genes in obese Asian Indians: a population-based study

BackgroundA population-based case control study was performed to determine the associations of Pro12Ala polymorphism in peroxisome proliferator-activated receptor-γ (PPARG) and Gly308Ala polymorphism in tumor necrosis factor-α (TNFA) genes in obese subjects.Patients and methodsOf 1,400 eligible subjects, ≧20 years, we recruited only 1,127. For extreme phenotype case-control design, we evaluated 201 subjects with body mass index (BMI) ≧30 kg/m2 (Group 1) and 143 with BMI <20 kg/m2 (Group 2). Clinical, anthropometric, biochemical, and nutritional details and polymorphisms were estimated.ResultsIn Group 1, the dietary intake of calories and fats was higher, physical activity was lower, and prevalence of truncal obesity, hypertension, high total cholesterol, low high-density lipoprotein cholesterol, and diabetes was greater than in Group 2. There were no homozygous polymorphisms of either gene. Heterozygous Pro12Ala polymorphism in PPARG was found in 15 (7.5%) subjects in Group 1 and 3 (2.1%) subjects in Group 2 (P = 0.028), and heterozygous Gly308Ala polymorphism in TNFA was found in 19 (9.5%) in Group 1 and 7 (4.9%) in Group 2 (P = 0.115). Presence of heterozygous polymorphism in PPARG and TNFA-predicted obesity with univariate odds ratio ([OR], 95% confidence intervals) of 2.25 (1.32–3.84, P = 0.003) and 1.48 (1.10–1.99, P = 0.009) and with multivariate OR 1.74 (1.03–2.93, P = 0.038) and 1.46 (1.05–2.03, P = 0.024), respectively. The addition of dietary and physical activity variables did not result in significant change.ConclusionObese Asian Indians have greater prevalence of heterozygous polymorphisms of Pro12Ala in PPARG and Gly308Ala in TNFA genes.

Evaluation of single nucleotide polymorphisms of Pro12Ala in peroxisome proliferator-activated receptor-&amp;gamma; and Gly308Ala in tumor necrosis factor-&amp;alpha; genes in obese Asian Indians: a population-based study

Evaluation of single nucleotide polymorphisms of Pro12Ala in peroxisome proliferator-activated receptor-γ and Gly308Ala in tumor necrosis factor-a genes in obese Asian Indians: a population-based study Namita Bhagat1,2, Mukta Agrawal1, Kalpana Luthra3, Naval K Vikram4, Anoop Misra4, Rajeev Gupta21Department of Home Science, University of Rajasthan, Jaipur, Rajasthan, India; 2Department of Medicine, Fortis Escorts Hospital, Jaipur, Rajasthan, India; 3Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India; 4Department of Medicine, All India Institute of Medical Sciences, New Delhi, IndiaBackground: A population-based case control study was performed to determine the associations of Pro12Ala polymorphism in peroxisome proliferator-activated receptor-γ (PPARG) and Gly308Ala polymorphism in tumor necrosis factor-α (TNFA) genes in obese subjects.Patients and methods: Of 1,400 eligible subjects, ≥20 years, we recruited only 1,127. For extreme phenotype case-control design, we evaluated 201 subjects with body mass index (BMI) ≥30 kg/m2 (Group 1) and 143 with BMI