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- Amu, Sylvie, 1978, et al.
(författare)
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Cytokines in the placenta of Pakistani newborns with and without intrauterine growth retardation
- 2006
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Ingår i: Pediatr Res. ; 59:2, s. 254-8
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Tidskriftsartikel (refereegranskat)abstract
- Although intrauterine growth retardation (IUGR) is a major risk factor for increased neonatal mortality and morbidity, the mechanisms behind it are not clear. We analyzed cytokine gene expression and gene polymorphisms in infants with and without IUGR in Pakistan, where IUGR is very common. 45 IUGR and 55 control mother/infant pairs were studied. mRNA for IL-10, IL-8, TNF-alpha, TGF-beta, IL-6, IL-4, IL-1beta, IL-12, IFN-gamma and GAPDH was quantified with RT-PCR from placenta. Cytokine and cytokine receptor gene polymorphisms for -1087IL10, -308TNFA, -174IL6, +915TGFB1, intron 2 IL1RN, +36TNFR1, 150V IL4RA and -159CD14 were determined from genomic DNA. The serum levels of IL-1beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha and TGF-beta were measured. There was a significant decrease of IL-10 and IL-12, but increase of TGF-beta in the decidua and similarly decrease of IL-10, but increase of TGF-beta in the trophoblasts of the IUGR placentas compared with the non-IUGR placentas. We found significantly lower levels of IL-1beta in serum from the mothers of the IUGR infants and of TGF-beta in serum of the infants with IUGR compared with the non-IUGR infants. We note that the IL-10 mRNA expression in the decidua was down-regulated, but the TGF-beta mRNA up-regulated in IUGR placentas of mothers from a population with multiple risk factors for IUGR. We propose that the low IL-10 in the placenta may be involved in the pathogenesis of IUGR and might possibly be treatable.
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| 4. |
- Donati, Mauro, 1966, et al.
(författare)
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Association of the -159 CD14 gene polymorphism and lack of association of the -308 TNFA and Q551R IL-4RA polymorphisms with severe chronic periodontitis in Swedish Caucasians.
- 2005
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Ingår i: Journal of clinical periodontology. - 0303-6979. ; 32:5, s. 474-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Severe forms of periodontitis are suggested to have a genetic basis. OBJECTIVE: The aim of the present investigation was to study the association of gene polymorphisms related to some immune regulation components (G-308A TNFA, Q551R IL-4RA and C-159T CD14) with severe chronic periodontitis. MATERIALS AND METHODS: Sixty patients (aged 36-74 years; mean 54.5+/-8.5) with severe and generalized chronic periodontitis were included. The patients exhibited bone loss >50% at all teeth. Thirty-nine periodontally healthy subjects between 35 and 78 years of age (mean 51.0+/-10.9) were recruited as controls. DNA was isolated from peripheral blood cells and genotyping was performed by combination of PCR and restriction endonuclease mapping. RESULTS: While gene polymorphisms for TNFA and IL-4RA did not show any association with severe chronic periodontitis, the analysis of the -159 CD14 gene polymorphism revealed significant differences between test and control groups. The proportion of subjects that exhibited the TT genotype was significantly smaller in the group with severe periodontitis than in periodontal healthy group (p=0.028; Fisher's exact test). The C allele carriage was 90% in the periodontitis group and significantly higher than in the healthy control group (72%). CONCLUSION: It is suggested that the -159 CD14 gene polymorphism is associated with chronic periodontitis in Caucasian subjects of a north European origin.
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| 5. |
- Donati, Mauro, 1966, et al.
(författare)
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Local expression of interleukin-10 and mCD14 in relation to the -1087 IL-10 and -159 CD14 gene polymorphisms in chronic periodontitis.
- 2008
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Ingår i: Journal of periodontology. - : Wiley. - 0022-3492 .- 1943-3670. ; 79:3, s. 517-24
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Associations between different gene polymorphisms and severe chronic periodontitis have been demonstrated. However, the influence of such genetic variations on the production of related proteins needs to be clarified. The aim of the present investigation was to study the local expression of interleukin (IL)-10 and membrane-bound CD14 (mCD14) in relation to the -1087 IL-10 and -159 CD14 gene polymorphisms in subjects with chronic periodontitis. METHODS: Fifty-three white subjects with generalized and severe chronic periodontitis volunteered. Twenty milliliters of blood was collected by venipuncture from each subject. DNA was isolated, and genotype analysis of the -1087 IL-10 and -159 CD14 gene polymorphisms was performed using polymerase chain reaction and restriction endonuclease mapping techniques. A gingival biopsy from one randomly selected diseased proximal site was also obtained from each subject. The biopsies were embedded, snap frozen, and prepared for immunohistochemical analysis. The inflammatory lesion was identified in the sections, and the proportions of IL-10+ and CD14+ cells were determined. RESULTS: The proportion of IL-10+ cells in the peripheral area of the periodontitis lesions was significantly larger in subjects with the -1087 IL-10 GG genotype than in subjects with the AG or AA genotype. However, the local expression of the mCD14 receptor did not vary between subjects with different -159 CD14 genotypes. CONCLUSIONS: It is suggested that IL-10 expression in chronic periodontitis lesions is associated with a distinct genotype. The observation adds to our understanding of interactions between genetic and environmental factors in the development of human diseases.
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| 6. |
- Gyllenberg, A, et al.
(författare)
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Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes
- 2012
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Ingår i: Genes and Immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 76:2, s. 202-203
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Tidskriftsartikel (refereegranskat)abstract
- The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.
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| 8. |
- Hesselmar, Bill, 1955, et al.
(författare)
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Interleukin-4 receptor polymorphisms in asthma and allergy: relation to different disease phenotypes.
- 2010
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Ingår i: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 99:3, s. 399-403
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Inheritance and genetic factors are supposed to influence susceptibility to asthma and allergy. We tested if single nucleotide polymorphisms (SNPs) in the IL4R gene were associated with susceptibility to such diseases, or if they were related to the phenotypic presentation of asthma and allergic rhinoconjunctivitis (ARC). Methods: Three hundred and nine 12- to 13-year-old children were included. Six SNPs in the IL4R were analysed in response to current allergic disease, and to presentation of specific asthma and ARC phenotypes. Questionnaires were used to determine allergic disease status, and skin prick tests to evaluate sensitization to common airborne allergens. Results: Less eczema was seen in individuals with the AA-genotype of rs2057768, and less ARC among those with the AA-genotype of rs2107356, especially ARC associated with sensitization to pollen. The AA-genotype of rs2057768 and the TT genotype of rs3024632 were associated with a specific asthma phenotype. Conclusion: Variations within the IL4R gene are associated with allergic diseases in children, preferably with eczema and disease phenotypes of ARC and asthma.
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| 9. |
- Svensson, Alexandra, 1978, et al.
(författare)
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A 3'-untranslated region polymorphism in the TBX21 gene encoding T-bet is a risk factor for genital herpes simplex virus type 2 infection in humans.
- 2008
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 89:Pt 9, s. 2262-8
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Tidskriftsartikel (refereegranskat)abstract
- It was recently shown that the transcription factor T-bet is crucial for adequate innate and acquired immune responses to genital herpes simplex virus type 2 (HSV-2) infection in mice. To test the possible genetic influence of variations in the TBX21 gene encoding T-bet on susceptibility to infection, this study evaluated the frequencies of five different single-nucleotide polymorphisms (SNPs) in the human TBX21 gene in 159 HSV-2-infected individuals and compared them with those in 186 healthy HSV-2-seronegative controls. The data showed that one variation (rs17244587) in the 3'-untranslated region of TBX21 was strongly associated with the incidence of genital HSV-2 infection. The frequency of the A allele at this position was 0.19 in the group of HSV-2-infected individuals compared with 0.05 in the group of uninfected controls (P=9.3x10(-8)). Furthermore, a homozygous AA genotype was found only among HSV-2-infected individuals and not in seronegative controls. These results indicate that the host genetic background may affect susceptibility to HSV-2 infection in humans, with TBX21 as a strong candidate gene.
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| 10. |
- Svensson, Alexandra, 1978, et al.
(författare)
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Polymorphisms in Toll-like receptor 3 confer natural resistance to human herpes simplex virus type 2 infection.
- 2012
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Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 93:Pt 8, s. 1717-24
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Tidskriftsartikel (refereegranskat)abstract
- Lack of Toll-like receptor 3 (TLR3) functional activity predisposes children to human herpesvirus 1 (HSV-1) encephalitis. In this study, we have investigated whether there is any link between TLR3 and adult HSV-2 infection by studying genetic variations in TLR3. The frequency of four single-nucleotide polymorphisms (SNPs) in the TLR3 gene in 239 patients with genital HSV-2 infection and 162 healthy controls, as well as the impact of these variants on TLR3 gene-expression levels, were compared. Two SNPs in the TLR3 gene (rs13126816 and rs3775291) were associated with a reduced incidence of HSV-2 infection. The minor allelic variants at both rs13126816 and rs3775291 were more common among healthy HSV-2-seronegative subjects than among HSV-2-infected individuals. This was even more apparent in HSV-1-seronegative individuals. There was, however, no association between any of the four TLR3 SNPs and HSV-2 disease severity, as they were expressed at similar proportions in asymptomatic and symptomatic HSV-2-infected patients alike. Furthermore, when assessing TLR3 mRNA expression in a limited number of HSV-2-infected individuals, we found that individuals carrying the homozygous genotypes for the minor alleles had significantly higher levels of TLR3 mRNA expression in peripheral blood mononuclear cells in response to HSV-2 stimulation than individuals that were homozygous for the major allele variants. Taken together, these results suggest that genetic variations in TLR3 may affect the susceptibility to HSV-2 infection in humans.
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