Sickle Cell Anemia
From SNPedia
First described clinically almost exactly 100 years ago, sickle cell anemia is an inherited blood disorder due to a SNP (rs334) in the beta globin HBB gene. It is found primarily in African and related populations.
The most common allele of rs334 is (A), encoding the Hb A form of (adult) hemoglobin. rs334(T) encodes the sickling form of hemoglobin, Hb S. Only individuals homozygous for this allele, in other words, having the rs334(T;T) genotype, will have sickle cell anemia. The (T) allele appears to have maintained through evolution due to the ~10 fold higher resistance to life-threatening forms of malaria that heterozygotes (rs334(A;T) genotypes) exhibit.
Sickle cell anemia has several clinical complications beyond the anemia usually arising early in life. These complications may be brought about by additional SNPs, and they include:
- Priapism, which can affect 30% of males with sickle cell anemia; SNPs found to be associated with this complication include [PMID 15638863]:
- Stroke, affecting perhaps 5% of sickle cell anemia patients; a model involving 6+ SNPs has been developed which claims high accuracy in estimating stroke risk for sickle cell anemia patients, involving at least these SNPs [PMID 15778708]:
- rs11853426, in the ANXA2 gene
- rs267196, in the BMP6 gene
- rs408505, also in the BMP6 gene
- rs3917733, in the SELP gene
- rs284875, in the TGFBR3 gene
- rs989554, in the ERG gene
- The genotypes for these 6 SNPs, in the order listed above and in orientation as in dbSNP, are predicted to have a risk for stroke within 5 years as follows:
- 0.007: CT, TT, TT, AG, AG, AG
- 0.060: CT, TT, TT, AG, GG, AG
- 0.185: TT, TT, CT, GG, GG, AA
- 0.727: TT, TT, CC, GG, GG, AA
- 0.868: CC, TT, CC, GG, GG, AA
- 0.968: CC, TT, CC, AG, GG, AA
- The genotypes for these 6 SNPs, in the order listed above and in orientation as in dbSNP, are predicted to have a risk for stroke within 5 years as follows:
