NcoI Polymorphisms Research Articles

Genetic Polymorphisms and Their Impact on Body Composition and Performance of Brazilians in a 105 Km Mountain Ultramarathon.

Although the studied polymorphisms affect muscular proteins, aerobic adaptations, and recovery, their influence on the anthropometric variables and performance in ultramarathon runners is still poorly understood. This study aimed to determine the influence of ACTN3 R577X, ACE I/D, and CK MM A/G NcoI polymorphisms on the changes in the anthropometric variables and running time of 105 km mountain runners, in which 22 male Brazilian elite athletes (35.9 ± 6.5 years) were evaluated. Genotyping of the R577X (RR, RX, and XX), ACE I/D (DD, ID, and II), and CK MM A/G Ncol (AA, AG, and GG) polymorphisms was performed using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique with DNA extracted from saliva. Body composition was determined via bioimpedance. Pre- and post-race weight differences were observed on athletes with the AA genotype (77.1 ± 5.9 kg; 74.6 ± 5.6 kg) compared with those with the AG genotype (74.5 ± 8.0 kg; 68 ± 5.1 kg) (p = 0.02; p = 0.02). The RR genotype showed a correlation between BMI and running time (R = 0.97; p = 0.004). The genotype II showed a correlation with % fat and fat mass concerning running time (R = 0.91; p = 0.003; R = 0.99; p < 0.0001). The AA genotype was associated with post-race weight and lean mass loss, while the RR genotype correlated with BMI, and the genotype II correlated with % body fat and fat mass in relation to times in the 105 km mountain ultramarathon.

LDL-R AvaII and NcoI Polymorphisms: An Indirect Risk Factor for Coronary Heart Disease Among a Mendelian Population of Delhi, India

AvaII and NcoI polymorphisms in the low-density lipoprotein receptor (LDL-R) gene are reported to alter cholesterol levels. Although found to be highly polymorphic worldwide, these mutations have not been validated in any Indian population. This case-control association study was conducted in an endogamous business community of Delhi. Blood samples from 100 cases and 100 age- and sex-matched controls belonging to the same ethnic group were subjected to biochemical and molecular analyses. Medical history and anthropometric measurements were taken from all the enrolled subjects. Linkage disequilibrium between the two polymorphisms was found to be significant (P = 0.0016). Significant variability was observed for the AvaII polymorphism among cases concerning waist-hip ratio, serum triglyceride, and low-density lipoprotein, which in turn was found to be associated with coronary heart disease.

Extended haplotype in the tumor necrosis factor gene cluster is associated with asthma and asthma-related phenotypes.

Tumor necrosis factor is a proinflammatory cytokine found in increased concentrations in asthmatic airways. The TNF-alpha (TNF) and lymphotoxin-alpha (LTA) genes belong to the TNF gene superfamily located within the human major histocompatibility complex on chromosome 6p in a region repeatedly linked to asthma. The TNF position -308 and LTA NcoI polymorphisms are believed to influence TNF transcription and secretion, respectively. This study sought to determine whether polymorphisms in TNF or LTA, or in TNF-LTA haplotypes, are associated with asthma and asthma phenotypes. We genotyped the TNF -308 and LTA NcoI polymorphisms, and two other haplotype-tagging polymorphisms in the TNF and LTA genes, in 708 children with mild to moderate asthma enrolled in the Childhood Asthma Management Program and in their parents. Using an extension of the family-based association tests in the PBAT program, each polymorphism was tested for association with asthma, age at onset of asthma, and time series data on baseline FEV(1) % predicted, postbronchodilator FEV(1) % predicted, body mass index, and log of PC(20). Although no associations were found for the individual single-nucleotide polymorphisms, the haplotype analysis found the LTA NcoI_G/LTA 4371T/TNF -308G/TNF 1078G haplotype to be associated with asthma and with all five phenotype groups. We conclude that it is unlikely that the TNF -308 or LTA NcoI polymorphisms influence asthma susceptibility individually, but that this haplotype of variants may be functional or may be in linkage disequilibrium with other functional single-nucleotide polymorphisms.

CYP1A1 and XRCC1 gene polymorphisms in SCC of the larynx.

The present study was undertaken to examine CYP1A1 and XRCC1 polymorphisms as potential genetic susceptibility markers for laryngeal squamous cell carcinoma (SCC). Eighty-eight patients with laryngeal SCC and 178 randomly selected healthy blood donors from the same Caucasian population (Porto, Northern Portugal) were analysed for CYP1A1 (MspI and NcoI) and XRCC1 (Arg194Trp and Arg399Gln) polymorphisms, using PCR-RFLP techniques. CYP1A1 MspI MH (mutant homozygous) and CYP1A1 NcoI HT (heterozygous) genotypes were more frequent in patients than in controls, with those carrying a CYP1A1 NcoI HT genotype having a 2.3-fold higher risk for tumour development. On the other hand, polymorphisms in XRCC1 codon 399 and codon 194 do not seem to play a role in the aetiology of smoking-related laryngeal SCC, once its distribution was similar in both analysed groups. All the significant associations observed were exclusively due to differences between controls and larynx glottic cancer patient subgroup. Furthermore, lower lifetime tobacco consumption was observed in laryngeal SCC patients carrying the MspI and NcoI polymorphisms, than in those who did not show the polymorphic variants. This investigation seems to support the importance of CYP1A1 gene polymorphism as a potential genetic marker of laryngeal cancer development, specially concerning smokers who have inherited the at-risk genotypes CYP1A1 MspI MH or CYP1A1 NcoI HT, who do appear to be more susceptible to the development of SCC of the glottic larynx.

Association analysis of HLA-Class iI and class iII gene polymorphisms in the susceptibility to mediterranean visceral leishmaniasis

HLA-DRB1, -DQB1, TNFα, TNFβ, HSP70-2 and HSP70-hom genetic polymorphisms were analyzed in 156 unrelated patients who developed mediterranean visceral leishmaniasis (MVL) due to Leishmania infantum, and 154 unrelated healthy controls, who have got asymptomatic infection with this parasite and were selected on the basis of a positive leishmanin skin test (LST). A signifi- cantly reduced frequency of HLA-DR2 was observed among MVL patients (16.1%), compared with controls (26.3%) (relative risk = 0.54; p = 0.04). HLA-DR2/DR13 as well as HLA-DQB1∗0201/- genotype frequencies were significantly lower in patients vs controls (relapse rate = 0.17 and 0.46, respectively; p < 0.05). However, using Bonferroni correction, none of these associations remained significant. No association was found, between either the −308 base pair TNFα gene polymorphism or the NcoI polymorphism in the first intron of the TNFβ gene and susceptibility to MVL. Analysis of PstI and NcoI polymorphisms in the coding region of HSP70-2 and HSP70-hom genes, respectively, revealed a significantly higher frequency of homozygotes for the HSP70-2/PstI negative allele, among patients (21.8%) vs controls (12.6%) (relapse rate = 1.94; p = 0.04). Again, this result was not significant after using Bonferroni correction. These results do not support association between susceptibility to MVL and the MHC class II and class III loci analyzed in this study.

Analysis of two human leukocyte antigen-linked polymorphic heat shock protein 70 genes in patients with severe sepsis.

To determine whether the genotype and allelic frequencies of two human leukocyte antigen-linked bi-allelic 70-kilodalton heat shock protein (HSP70) gene polymorphisms are associated with susceptibility to and outcome of severe sepsis. Furthermore, we investigated a possible linkage between HSP70 gene polymorphisms and the previously reported and mortality-related tumor necrosis factor-beta (TNF-beta) NcoI gene polymorphism. Consecutive entry study of patients with severe sepsis. Surgical intensive care unit in a university hospital. Eighty-seven patients with a diagnosis of severe sepsis. None. We studied two bi-allelic polymorphisms within the coding region of the constitutively expressed HSP70-HOM C/T, and the stress-inducible HSP70-2 G/A in patients with severe sepsis. The HSP70-HOM Ncol, HSP70-2 Pstl, and TNF-beta NcoI polymorphisms were identified by means of the polymerase chain reaction followed by restriction analysis of the polymerase chain reaction product. No significant differences in genotype and allelic frequencies were observed for both HSP70 gene polymorphisms between the 87 patients and the 110 healthy Caucasians serving as the control group. In addition, no differences in genotype and allelic frequencies between surviving and nonsurviving patients were detected. The allelic frequencies in the group of nonsurvivors were 0.8 for the HSP70-HOM C allele and 0.2 for the HSP70-HOM T allele vs. 0.87 and 0.13 for the survivors (p > .05). The frequency for the HSP70-2 G allele was 0.36 and 0.64 for the HSP70-2 A allele in the group of nonsurvivors vs. 0.41 and 0.59 for the survivors (p > .05). Analysis of a possible linkage between HSP70 and TNF-beta genotypes resulted in a significant association (odds ratio, 4.15; p < .01) of the HSP70-2 A/A homozygous genotype and the TNFB2/B2 homozygous genotype, which is reported to be a genomic marker for a poor prognosis in severe sepsis. Our data show that the bi-allelic NcoI and PstI polymorphisms within the HSP70-HOM and HSP70-2 locus, respectively, are associated with neither susceptibility to nor outcome of severe sepsis. Moreover, we found a linkage between HSP70-2 A homozygotes and the previously reported and mortality-related homozygous genotype, TNFB2/B2, in patients suffering from severe sepsis.

Myasthenia gravis and tumor necrosis factor β polymorphisms: linkage disequilibrium but no association beyond HLA-B8

Tumor necrosis factor (TNF) may contribute to the susceptibility for autoimmune diseases. We examined TNFβ gene polymorphisms detected by AspHI and NcoI digestion of genomic DNA in patients with myasthenia gravis ( n=105) and healthy controls ( n=114). In both groups, the frequencies of TNFβ alleles were not different. AspHI and NcoI polymorphisms of TNFβ showed a strong association with HLA-B8 ( p<0.03 resp. p<0.0001 for AspHI and NcoI) both in patients and controls. Our results imply linkage disequilibrium of TNFβ alleles with HLA-B8 and in myasthenia gravis we were unable to show a stronger association beyond HLA-B8.

A novel NcoI polymorphism creates a fifth haplotype in the 3' untranslated region of CKM.

A novel NcoI polymorphism has been detected in the 3' untranslated region of the creatinine kinase (CKM) gene. The addition NcoI restriction site creates a fifth haplotype for the NcoI and TaqI restriction fragments length polymorphisms at this locus, and segregates with the myotonic dystrophy gene in 3 generations of an affected family.