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Evaluation of interleukin 28B single nucleotide polymorphisms in infants suffering from bronchiolitis.

ABSTRACT: The genetic diversity of the host is believed to be the key of the diversity in the clinical presentation of bronchiolitis. The aim of this study was to determine whether the known rs12979860 and rs8099917 single nucleotide polymorphisms (SNPs) in interleukin (IL)28B region, influence clinical features and natural history of bronchiolitis. Both SNPs showed no significant association with the risk of hospitalization for respiratory syncytial virus (RSV), viral load, disease severity, and other clinical features of patients. Interestingly infants carrying IL28B rs12979860 TT genotype had lower age at hospital admission than that of infants carrying CC/CT genotypes. Overall our results indicate that both IL28B SNPs had no impact on the clinical course of bronchiolitis with the only exception of the IL28B rs12979860 SNP which increased the risk of hospitalization for bronchiolitis at early age.

SUBMITTER: Scagnolari C

PROVIDER: S-EPMC7114428 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Evaluation of interleukin 28B single nucleotide polymorphisms in infants suffering from bronchiolitis.

Scagnolari Carolina C Midulla Fabio F Riva Elisabetta E Monteleone Katia K Solimini Angelo A Bonci Enea E Cangiano Giulia G Papoff Paola P Moretti Corrado C Pierangeli Alessandra A Antonelli Guido G

Virus research 20120225 2

The genetic diversity of the host is believed to be the key of the diversity in the clinical presentation of bronchiolitis. The aim of this study was to determine whether the known rs12979860 and rs8099917 single nucleotide polymorphisms (SNPs) in interleukin (IL)28B region, influence clinical features and natural history of bronchiolitis. Both SNPs showed no significant association with the risk of hospitalization for respiratory syncytial virus (RSV), viral load, disease severity, and other cl ...[more]

PMID: 22374338

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Project description:INTRODUCTION:Recent studies have demonstrated the role of the interleukin 28B (IL28B) polymorphisms in predicting treatment induced and spontaneous clearance from Hepatitis C virus (HCV) infection, suggesting the possibility of tailored therapy in HCV infected patients. Genome-wide association studies have shown that single nucleotide polymorphisms (SNPs) near IL 28B gene on chromosome 19 are strong predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin. This study was aimed at analyzing the co-prevalence of two common and clinically significant SNPs in a cohort of Ligurian patients. METHODS:Two SNPs (rs12979860, rs8099917) were genotyped in the IL28B locus from 175 DNA samples collected from HCV-infected consecutive patients in a Laboratory of Liguria Region, northern Italy. A real-time polymerase chain reaction in a Corbett Research Termocycler (Rotor Gene 3000A) by fluorescent probes (Fast Set IL 28B, Arrow Diagnostics) was used for the detection, according to the manufacturer's instructions. RESULTS:Carriers of rs12979860CT genotype predominated (87/175, 50%), homozygotes for allele C were 68/175 (39%) and the remaining were homozygotes for IFN-resistant allele T (11%). As for the rs8099917 SNP, genotypes were thus distributed: 96/175 (55%) carried the rs8099917 TT genotype, whereas 70/175 (40%) and 9/175 (5%), were heterozygotes or homozygotes for the G allele. The variants rs12979860CC and rs8099917TT were found in 39% and 54% of overall patients with HCV genotype 1, respectively. The combined assessment of examined SNPs resulted in three most prevalent genotypes (rs12979860CC/rs8099917TT, rs12979860CT/rs8099917TG and rs12979860CT/rs8099917TT) with a frequency of 35%, 31% and 18%, respectively. DISCUSSION:Recent findings demonstrated that in carriers of rs12979860CT the determination of additional genotype of rs8099917 SNP could significantly improve the prediction of SVR. In our study cohort carriers of rs12979860CT represented 50% of all patients, who could take advantage with respect to SVR prediction by further determination of the rs8099917 SNP. The simultaneous genotyping of two IL28B SNPs should thus be recommended in HCV infected patients prior to treatment initiation.

Project description:AIM:To analyze the role of rs12979860 and rs8099917 polymorphisms in hepatitis C virus (HCV) genotype 1 infection of Brazilians. METHODS:A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C (CHC) who had completed a 48-wk regimen of pegylated-interferon ?-2a or -2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and 199 healthy blood donors (controls) from a single site between January 2010 and January 2012. Data on the patients' response to treatment was collected. Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin (IL)28B gene fragment encompassing the single nucleotide polymorphisms (SNPs) rs12979860 (C/T) and rs8099917 (T/G) was carried out for 79 of the CHC patients and 199 of the controls. Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients. RESULTS:SNP rs12979860 genotyping was successful in 99.5% of the controls and 97.2% of the CHC patients, whereas the SNP rs8099917 genotyping was successful in 95.5% of the controls and 100% of the CHC patients. The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups, with significantly higher genotype frequencies of CC and TT in the controls (P = 0.037 and 0.046, respectively) and of TT and GG in the CHC patients (P = 0.0009 and 0.0001, respectively). Analysis of the CHC patients who achieved sustained virological response (SVR) to treatment (n = 55) indicated that the rs12979860 C allele and CC genotype were predictors of SVR (P = 0.02). No significant correlation was found between rs8099917 genotypes and treatment response, but carriers of the T allele showed significantly higher rates of SVR (P = 0.02). Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917 (P = 0.07). CONCLUSION:The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCV-infected individuals may indicate a potential protective role for these IL28B-related polymorphisms.

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Evaluation of interleukin 28B single nucleotide polymorphisms in infants suffering from bronchiolitis.

Publications

Evaluation of interleukin 28B single nucleotide polymorphisms in infants suffering from bronchiolitis.

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