Homozygosis for (12) CA repeats in the first intron of the human IFN‐<i>γ</i> gene is significantly associated with the risk of aplastic anaemia in Caucasian population

Some acquired aplastic anemia (AA) results from immune‐mediated destruction of hematopoietic stem cells. Cytokine gene polymorphisms are implicated in controlling cytokine production and increasing the susceptibility to some autoimmune diseases. We characterized the IL‐6/‐174, TNF‐α/−308, IL‐10/−1082, IFN‐γ/+874, TGFβ1/−509 single nucleotide polymorphisms (SNP's) and the IL1‐RA second intron variable number tandem repeat (VNTR) alleles in 73 patients with AA and compared the frequency of genotypes to established control populations. We found that some patients with acquired AA have polymorphisms which are linked to high production of proinflammatory cytokines, particularly TNF‐α and IFN‐γ. Am. J. Hematol., 2007. Published 2007 Wiley‐Liss, Inc.

show abstract

“…Similarly, genotype (CA) 12-12 (homozygosis for allele no. 2) was more frequent in 67 Caucasian AA patients [20].…”

Section: Resultsmentioning

confidence: 95%

Cytokine gene polymorphisms in acquired bone marrow failure

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Immune-mediated T-cell destruction of the bone marrow has been shown both in vitro and in vivo, but the reason for T-cell activation in these patients is not clear. A combination of genetic risk factors, including SNPs in tumor necrosis factor-alpha (Demeter et al 2002;Peng et al 2003) and gamma-interferon (Dufour et al 2004) may be contributory.…”

Section: Acquired Aplastic Anemiamentioning

confidence: 99%

The role of telomere biology in bone marrow failure and other disorders

Savage

Alter

2008

Mechanisms of Ageing and Development

View full text Add to dashboard Cite

Telomeres, consisting of nucleotide repeats and a protein complex at chromosome ends, are essential in maintaining chromosomal integrity. Dyskeratosis congenita (DC) is the inherited bone marrow failure syndrome (IBMFS) that epitomizes the effects of abnormal telomere biology. Patients with DC have extremely short telomere lengths (<1 st percentile) and many have mutations in telomere biology genes. Interpretation of telomere length in other IBMFSs is less straightforward. Abnormal telomere shortening has been reported in patients with apparently acquired hematologic disorders, including aplastic anemia, myeolodysplasia, paroxysmal nocturnal hemoglobinuria, and leukemia. In these disorders, the shortest lived cells have the shortest telomeres, suggestive of increased hematopoietic stress. Telomeres are also markers of replicative and/or oxidative stress in other complex disease pathways, such as inflammation, stress, and carcinogenesis.The spectrum of related disorders caused by mutations in telomere biology genes extends beyond classical DC to include marrow failure that does not respond to immunosuppression, idiopathic pulmonary fibrosis, and possibly other syndromes. We suggest that such patients are categorized as having an inherited disorder of telomere biology. Longitudinal studies of patients with very short telomeres but without classical DC are necessary to further understand the long-term sequelae, such as malignancy, osteonecrosis/osteoporosis, and pulmonary and liver disease.

show abstract

“…3 Polymorphisms in cytokine genes, associated with an increased immune response, are also more prevalent in AA. 4 Constitutive expression of T-bet, a transcriptional regulator that is critical to Th1 polarization, is present in the majority of AA patients. 5 Genome-wide transcriptional analysis of T cells from AA patients has implicated some components of innate immunity in AA, including Toll-like receptors and natural killer cells.…”

Section: Introductionmentioning

confidence: 99%