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Background and Objectives : Genomic scan analyses have suggested that the chemokine receptor cluster (CCR2, CCR3, CCR5 < 300 kb span) on the short arm of chromosome 3 may contribute to susceptibility to HIV-1 infection and to the expression of a number of inflammatory diseases. Two single nucleotide polymorphisms (SNP) and a deletion in these chemokine receptors have also been found in case-control studies to be associated with susceptibility for asthma and related phenotypes. We extended these case-control studies by establishing whether these polymorphisms were in linkage and linkage disequilibrium with asthma and related phenotypes using linkage and haplotype analyses. Methods : We genotyped 154 nuclear families identified through two child probands with physician-diagnosed asthma (453 unrelated individuals) including 303 unrelated parents and 150 unrelated children. Atopy was defined as a positive skin prick test (SPT 3 mm) to a panel of common inhaled allergens. Results : From a panel of ten known SNPs, only three polymorphisms: -G190A in CCR2, -T51C in CCR3, and a 32 bp deletion in CCR5 were found to occur at clinically relevant frequencies. All 154 families were used for haplotype analysis but only 12 nuclear families were eligible for linkage analysis. Both analyses confirmed that the mutations were in linkage with asthma, but not with atopy. Conclusion : The chemokine receptor genes on 3p21.3 are significantly plausible candidate genes that can influence the expression of asthma. The previous association of the CCR5∆32 deletion with protection from childhood asthma appears to be explained by linkage disequilibrium with the -G190A mutation in the CCR2 receptor gene.

Background: Asthma is a multifactorial inherited disease. Many potential candidate genes have been identified to date including the chemokine RANTES promoter (17q11.2). It has been reported that -403 RANTES polymorphism is associated with increasing the severity of airway obstruction and persistent airway inflammation. Objective: To assess the contribution of this candidate using two different linkage/association and case-control analyses. Methods: 105 nuclear families (420 individuals) with at least two affected children with physician-diagnosed asthma (PDA) were genotyped using the RFLPPCR method. Asthma severity was determined as: mild — inhaled beta-2 agonist only, or moderate/severe — requiring regular inhaled corticosteroids. Results: 43 families with at least one parent heterozygous for-403 G/A RANTES gene were eligible for (TDT) and (PDT). Overall allele frequency for -403 was 38.3% and transmission of -403 allele was highly significant with PDT (p=0.0056), but not significant with TDT (p=0.2302). Case-control analysis in children 624y [median 14y] revealed a significant association of-403NG with asthma (p=0.013) but no significant differences between severity categories. In parents aged 34-61y [median 42y] a reverse significant association was observed (p=0.016). Conclusions: -403 G/A RANTES polymorphism is significantly associated with asthma in children and young adults but with no or even reverse associations for middle aged adults. [ABSTRACT FROM AUTHOR]

According to findings, long non-coding RNAs (lncRNAs) have an important function in the onset and growth of various cancers, including rectal cancer (RC). RC offers unique issues in terms of diagnosis, treatment, and results, needing a full understanding of the cellular mechanisms that cause it to develop. This thorough study digs into the various functions that lncRNAs perform in RC, giving views into their multiple roles as well as possible therapeutic consequences. The function of lncRNAs in RC cell proliferation, apoptosis, migratory and infiltrating capacities, epithelial-mesenchymal shift, and therapy tolerance are discussed. Various lncRNA regulatory roles are investigated in depth, yielding information on their effect on essential cell functions such as angiogenesis, death, immunity, and growth. Systemic lncRNAs are currently acknowledged as potential indications for the initial stages of identification of cancer, with the ability to diagnose as well as forecast. Besides adding to their diagnostic utility, lncRNAs offer therapeutic opportunities as actors, contributing to the expanding landscape of cancer research. Moreover, the investigation looks into the assessment and predictive utility of lncRNAs as RC markers. The article also offers insight into lncRNAs as chemoresistance and drug resistance facilitators in the setting of RC. [ABSTRACT FROM AUTHOR]

Objective: To examine the possible associations between CCR5delta32 and asthma and related phenotypes in high-risk families., Methods: A total of 154 families (453 individuals), with at least two affected children with physician-diagnosed asthma (PDA) and atopy defined as one or more skin prick test to common inhaled allergen (SPT wheal > or = 3 mm), were studied. Samples were genotyped using PCR assay and tested for possible associations by TDT and PDT and case control analyses., Results: Overall allelic frequency for CCR5delta32 was 26.1%, and both TDT and PDT demonstrated similar nonsignificant associations (p=0.123) and (p=0.088). Analysis by the clinical categories of non atopic and atopic asthma and presence or absence of atopy without asthma failed to identify any significant associations. However there were strong associations of the mutant allele with the phenotypes of negative SPT, PC 20 less than 8 mg/ml, baseline FEV1 greater than the population median (83.5% predicted) and serum IgE less than 100 IU/l for child probands but only for negative SPT in unrelated parents., Conclusion: Non-significant association was seen with family based association tests (FBATs). The strong associations with the asthma related phenotypes in child probands support previous observations that CCR5 is in linkage disequilibrium with CCR2 or CCR3.

Objective: To explore a possible association between the major functional CCR2V64I polymorphism and asthma and related phenotypes independent of atopy., Methods: We conducted this study in the Royal Aberdeen Children's Hospital, University of Aberdeen Medical School, United Kingdom from September 2004 to December 2006. One hundred and fifty-four unrelated nuclear families (598 individuals including children and parents) were identified from the local Grampian population. The major functional polymorphism CCR2V64I was analyzed for associations with asthma, lung function (forced expiratory volume% [FEV1%] of predicted), bronchial hyperresponsiveness (BHR) to methacholine, total serum-immunoglobulin E (s-IgE) and allergic sensitization (positive skin prick test to common allergens) in 154 asthmatic families., Results: Pedigree disequilibrium test and case control analyses showed that the CCR2V64I polymorphism was significantly associated with the absence of asthma FEV1%, predicted above the population median of 83%, but not with s-IgE levels or specific sensitization., Conclusion: We identified associations between the V-64I CCR2 polymorphism and protection against asthma, higher FEV1, and absence of BHR in families at high risk of asthma and atopy, suggesting an important role for the CCR2 receptor in modulating airway inflammation independent of atopy.