Cytokine gene polymorphisms in preterm infants with necrotising enterocolitis: genetic association study

BACKGROUND The inflammatory cytokine cascade is implicated in the pathogenesis of necrotising enterocolitis (NEC). Genetic association studies of cytokine polymorphisms may help to detect molecular mechanisms that are causally related to the disease process. AIM To examine associations between the common genetic variants in candidate inflammatory cytokine genes and NEC in preterm infants. METHODS Multi-centre case-control and genetic association study. DNA samples were collected from 50 preterm infants with NEC and 50 controls matched for gestational age and ethnic group recruited to a multi-centre case-control study. Ten candidate single-nucleotide polymorphisms in cytokines previously associated with infectious or inflammatory diseases were genotyped. The findings were included in random-effects meta-analyses with data from previous genetic association studies. RESULTS All allele distributions were in Hardy-Weinberg equilibrium. None of the studied cytokine polymorphisms was significantly associated with NEC. Four previous genetic association studies of cytokine polymorphisms and NEC in preterm infants were found. Meta-analyses were possible for several single-nucleotide polymorphisms. These increased the precision of the estimates of effect size but did not reveal any significant associations. CONCLUSIONS The available data are not consistent with more than modest associations between these candidate cytokine variant alleles and NEC in preterm infants. Data from future association studies of these polymorphisms may be added to the meta-analyses to obtain more precise estimates of effects sizes.The study was funded by Tenovus (Scotland)

Interleukin-18 gene promoter polymorphisms and recurrent spontaneous abortion

Background: IL-18 is a multifunctional cytokine capable of inducing either Th1 or Th2 polarization depending on the immunologic milieu. IL-18 is detected at the materno-fetal interface very soon in early pregnancy. Two polymorphisms in the promoter region of the IL-18 gene at positions of -607 and -137 appear to have functional impacts. Objective: This study attempts to evaluate the frequency of these two polymorphisms in the IL-18 gene promoter in patients with recurrent spontaneous abortion (RSA) and normal pregnant women. Subjects and methods: One hundred and two RSA patients and 103 healthy pregnant women were enrolled in this study. Single nucleotide polymorphisms of the IL-18 gene at positions -607 (C/A) and -137 (G/C) were analyzed by the sequence-specific PCR method. Results: There was no significant association between the allele, genotype, and haplotype frequencies of the two single nucleotide polymorphisms (SNPs) in the IL-18 gene promoter and RSA. Conclusion: The results of this study showed that IL-18 gene promoter polymorphisms at positions -607 and -137 did not confer susceptibility to RSA in southern Iranian patients. © 2006 Elsevier Ireland Ltd. All rights reserved

Single nucleotide polymorphisms from Theobroma cacao expressed sequence tags associated with witches' broom disease in cacao

In order to increase the efficiency of cacao tree resistance to witches¿ broom disease, which is caused by Moniliophthora perniciosa (Tricholomataceae), we looked for molecular markers that could help in the selection of resistant cacao genotypes. Among the different markers useful for developing marker-assisted selection, single nucleotide polymorphisms (SNPs) constitute the most common type of sequence difference between alleles and can be easily detected by in silico analysis from expressed sequence tag libraries. We report the first detection and analysis of SNPs from cacao-M. perniciosa interaction expressed sequence tags, using bioinformatics. Selection based on analysis of these SNPs should be useful for developing cacao varieties resistant to this devastating disease. (Résumé d'auteur

Relationships Among Beef Cow Productivity Traits and Single Nucleotide Polymorphisms in the Bovine Heat Shock Protein 70 Gene

When eukaryotes are exposed to stressors such as heat, toxins, and low oxygen levels, heat shock proteins (HSPs) are synthesized to maintain normal cellular function within the body. Single nucleotide polymorphisms in the heat shock protein 70 (Hsp70) gene have been associated with calving percentage, and Julian calving date in spring-calving crossbred Brahman cows (Rosenkrans, et al., 2010). Our objective was to determine associations between previously identified polymorphisms in the promoter region and coding sequence of the bovine Hsp70 gene and beef cow efficiency. We evaluated productivity traits, including Julian calving date and calving rates, of fall-calving cows at each single nucleotide polymorphism (SNP) site. Genomic DNA was extracted from blood samples collected from crossbred cows (n=109) and amplified by polymerase chain reaction (PCR) using specific forward and reverse primers. Upon amplification, samples were purified, quantified, and sequenced in a commercial laboratory. Sequences were analyzed to determine SNP and genotypes were assigned to each of them. Production data of the cows from 2012-2014 were analyzed at each SNP site. Cows with CD genotype at C895D calved about one week later (P = 0.0001) and tended (P \u3c 0.06) to have calves with lighter birth weights compared to cows with CC genotype. Genotype at G2033C affected (P \u3c 0.02) weaning weight and cow efficiency. Genotype of a haplotype composite (No SNP, Deletion, and Yes SNP) affected (P \u3c 0.02) Julian date and cow efficiency. Polymorphisms associated with the bovine Hsp70 gene were related to important cattle productivity characteristics. Selecting replacement cattle with known Hsp70 genotypes may result in herds that are more thermotolerant and sustainable

MMP-2 geno-phenotype is prognostic for colorectal cancer survival, whereas MMP-9 is not.

The prognostic significance of single-nucleotide polymorphisms (SNPs) and tumour protein levels of MMP-2 and MMP-9 was evaluated in 215 colorectal cancer patients. Single-nucleotide polymorphism MMP-2(-1306T) and high MMP-2 levels were significantly associated with worse survival. Extreme tumour MMP-9 levels were associated with poor prognosis but SNP MMP-9(-1562C>T) was not. Tumour MMP levels were not determined by their SNP genotypes

XRCC1, but not APE1 and hOGG1 gene polymorphisms is a risk factor for pterygium.

PurposeEpidemiological evidence suggests that UV irradiation plays an important role in pterygium pathogenesis. UV irradiation can produce a wide range of DNA damage. The base excision repair (BER) pathway is considered the most important pathway involved in the repair of radiation-induced DNA damage. Based on previous studies, single-nucleotide polymorphisms (SNPs) in 8-oxoguanine glycosylase-1 (OGG1), X-ray repair cross-complementing-1 (XRCC1), and AP-endonuclease-1 (APE1) genes in the BER pathway have been found to affect the individual sensitivity to radiation exposure and induction of DNA damage. Therefore, we hypothesize that the genetic polymorphisms of these repair genes increase the risk of pterygium.MethodsXRCC1, APE1, and hOGG1 polymorphisms were studied using fluorescence-labeled Taq Man probes on 83 pterygial specimens and 206 normal controls.ResultsThere was a significant difference between the case and control groups in the XRCC1 genotype (p=0.038) but not in hOGG1 (p=0.383) and APE1 (p=0.898). The odds ratio of the XRCC1 A/G polymorphism was 2.592 (95% CI=1.225-5.484, p=0.013) and the G/G polymorphism was 1.212 (95% CI=0.914-1.607), compared to the A/A wild-type genotype. Moreover, individuals who carried at least one C-allele (A/G and G/G) had a 1.710 fold increased risk of developing pterygium compared to those who carried the A/A wild type genotype (OR=1.710; 95% CI: 1.015-2.882, p=0.044). The hOGG1 and APE1 polymorphisms did not have an increased odds ratio compared with the wild type.ConclusionsXRCC1 (Arg399 Glu) is correlated with pterygium and might become a potential marker for the prediction of pterygium susceptibility

Evidence of uneven selective pressure on different subsets of the conserved human genome : implications for the significance of intronic and intergenic DNA

Peer reviewedPublisher PD

No association of CTLA-4 polymorphisms with susceptibility to Behcet disease

Background: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a key negative regulator of T lymphocytes and has been shown to be associated with a number of autoimmune diseases. The present study was performed to assess the association between CTLA-4 polymorphisms and Behcet disease (BD) in Chinese patients. Methods: Two hundred and twenty-eight BD patients and 207 controls were analysed for four single nucleotide polymorphisms (SNPs) (21661A/G, 2318C/T, + 49G/A and CT60G/A) in the CTLA-4 gene by PCR-restriction fragment length polymorphism (RFLP) analysis. The association between SNP +49A/G and BD in Chinese population as well as other ethnic groups was analysed by meta-analysis. Results: No association could be detected between CTLA-4 SNPs or haplotypes and BD. Also, no association was observed between CTLA-4 polymorphisms and BD subgroups, stratified by clinical features. A meta-analysis showed that there was no heterogeneity between studies (p = 0.60, I-2 = 0%) and that CTLA-4 SNP + 49 was not associated with BD (overall effect: Z = 0.26, p = 0.79). Conclusion: This study and a meta-analysis failed to demonstrate any association between the tested CTLA-4 polymorphisms and B