| related to sickle cell anemia |
| Geno
|
Mag
|
Summary
|
| (C;C)
|
0.5
|
common, increased risk for sickle cell leg ulcers
|
| (C;T)
|
0.5
|
lower risk
|
| (T;T)
|
0.5
|
lower risk
|
rs736893 is related to sickle cell anemia, a genetic disease in which red blood cells form an abnormal crescent shape as opposed to the normal disc shape [1]. In the United States, it's estimated that sickle cell anemia affects 70,000–100,000 people, mainly African Americans. A New England Journal of Medicine study conducted in the US reported an average life expectancy of 42 in males and 48 in females [PMID 7993409].
The landmark 1949 Science paper titled "Sickle Cell Anemia, a Molecular Disease by Pauling established the molecular basis for this sickle cell anemia and introduced notions that will become central to molecular medicine. Sickle cell leg ulcers are common complications of sickle cell anemia [PMID 1905464]. As of 2010, despite the fact that this complication has been recognized since the early times of sickle cell disease, there has been little improvement in the efficacy of its management and clinical outcome over the past 100 years [PMID 20872960
].
[16681647?dopt=Abstract PMID 16681647] In a study, investigators found significant associations between rs736839 (18q21.1) and sickle cell leg ulcers. Using the Benjamini and Hochberg algorithm to control FDR, this SNP was the only one found with FDR under 10%. In this study, the odds ratio for rs736893 was 1.95, with 95% confidence interval of (1.35–2.82). Homozygous C is associated with elevated levels of risk for sickle cell leg ulcers. In contrast, having at least one of T is considered less risky. This case-control study involved 387 cases and 920 controls. The genotype associations were adjusted for sex and age because men and older individuals are more likely to be afflicted [2475188?dopt=Abstract PMID 2475188].
Although not in a gene, rs736839 is adjacent to SMAD7, which is part of the Transforming Growth Factor–b/Bone Morphogenetic Protein (TGF-beta/BMP) pathway. In a separate case-control SNP association study, IGF1R and genes in the TGF-beta / BMP pathway has been linked to sickle cell anemia [16886151?dopt=Abstract PMID 16886151].
The Transforming growth factor beta (TGF-beta) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, apoptosis, cellular homeostasis and other cellular functions. In spite of the wide range of cellular processes that the TGF-beta signaling pathway regulates, the process is relatively simple. TGF-beta superfamily ligands bind to a type II receptor, which recruits and phosphorylates a type I receptor. The type I receptor then phosphorylates receptor-regulated SMADs (R-SMADs) which can now bind the coSMAD SMAD4. R-SMAD/coSMAD complexes accumulate in the nucleus where they act as transcription factors and participate in the regulation of target gene expression. [2]
[PMID 20401335] Sickle Cell Disease in the Post Genomic Era: A Monogenic Disease with a Polygenic Phenotype.
].
