A Polymorphism in the IL-5 Gene is Associated with Inhibitor Development in Severe Hemophilia A Patients

Abstract

Objective: A severe complication in the replacement therapy of hemophilia A (HA) patients is the development of alloantibodies (inhibitors) against factor VIII, which neutralizes the substituted factor. The primary genetic risk factors influencing the development of inhibitors are F8 gene mutations. Interleukins and cytokines that are involved in the regulation of B-lymphocyte development are other possible targets as genetic risk factors. This study assesses the possible involvement of 9 selected single nucleotide gene polymorphisms (SNPs) with interleukins (IL-4, IL-5, and IL-10), transforming growth factor beta 1 (TGF-β1), and interferon gamma (IFN-γ) in inhibitor development in severely affected HA patients carrying a null mutation in the F8 gene. Materials and Methods: A total of 173 HA patients were screened for intron 22 inversion and null mutations (nonsense and deletions). Genotyping of a total of 9 SNPs in genes IL-4, IL-5, IL-10, TGF-β1, and IFN-γ in 103 patients and 100 healthy individuals was carried out. Results: An association analysis between 42 inhibitor (+) and 61 inhibitor (-) patients showed a significant association with the T allele of rs2069812 in the IL-5 gene promoter and patients with inhibitors (p=0.0251). The TT genotype was also significantly associated with this group with a p-value of 0.0082, odds ratio of about 7, and confidence interval of over 90%, suggesting that it is the recessive susceptibility allele and that the C allele is the dominant protective allele. Conclusion: The lack of other variants in the IL-5 gene of patients and controls suggests that rs2069812 may be a regulatory SNP and may have a role in B-lymphocyte development, constituting a genetic risk factor in antibody development.

Association of Interleukin-10 gene promoter polymorphisms with obstructive sleep apnea

“…hapmap.org and http:www.ncbi.nlm.nih.govsnp). Although the allele frequencies of IL-10 promoter polymorphisms found in healthy controls in our study were different from the prevalence rates reported in different regions of the The dendrogram demonstrates the nature of the interactions between polymorphisms There was a synergistic interaction, with the strongest interaction between the IL-10 (−1082 G/A) and (−592 C/A) polymorphisms world, they were similar to some previous studies performed in Turkish population [35,36]. These discrepancies in the minor allele frequencies of IL-10 promoter polymorphisms between healthy individuals demonstrated the importance of both ethnic and geographic diversity and sample size to evaluate study results in the genetic association studies [37].…”

Combinations of Interleukin-10 Gene Promoter Polymorphisms with -1082A, -819T, -592A Minor Allele are Associated with Sinonasal Polyposis

“…In this study, DNA sequence analysis of the IL-10 gene's promoter in patients with SP revealed 32% of position -1082 guanine into adenine (c. Despite the fact that the global prevalence notified of the allele frequencies of -1082, -819, and -592 SNPs in IL-10 gene in control groups vary, and they are same to last studies in Turkish society [13,21,22].…”

“…In this study, the IL-10 gene SNPs -1082, -819, -592 and their genotypic combinations in 100 SP patients and 100 volunteer-healthy controls in the Turkish population were Wide variation has been also recorded in the frequencies of IL-10 gene's promoter SNPs among distinct populations. Despite the fact that the global prevalence notified of the allele frequencies of -1082, -819, and -592 SNPs in IL-10 gene in control groups vary, and they are same to last studies in Turkish society [13,21,22].…”

FVIII inhibitors: pathogenesis and avoidance

“…These are summarized in Table 1. [40][41][42][43][44][45][46][47][48][49][50][51][52] Based on current understanding, it seems unlikely that a single marker of significantly greater importance than multiple others will be identified. In fact, the associations found between polymorphic genes and inhibitory antibodies have not been consistent across study cohorts, and the question, of course, is why?…”