|(C;C)||0||C1 subtype of transferrin; common in clinvar|
|(C;T)||1.1||Heterozygote carrying both C1 and C2 transferrin subtypes; very slightly higher risk for Alzheimers|
|(T;T)||1.2||C2 transferrin subtype; very slightly higher risk for Alzheimers|
rs1049296, also known as Pro570Ser, is best known as the basis for the C1/C2 subtypes of the transferrin TF gene. The rs1049296(C) allele encodes the C1 subtype, and the rarer rs1049296(T) allele encodes the C2 subtype.
Involved in the transport of iron, transferrin and its subtypes have been linked at times to various conditions, perhaps most notably Alzheimer's disease. One meta-analyis of 19 studies with 6310 cases and 13661 controls concluded that the C2 allele, rs1049296(T), was associated with slightly increased risk for Alzheimer's, with odds ratios around 1.1-1.2.[PMID 23968943]
Pathogens may scavenge iron, and the body's attempts to sequester it from such pathogens are a form of defense termed nutritional immunity. One explanation for the presence of the C2 TF subtype in humans is that it may reduce the effectiveness of some bacterial transferrin binding proteins.10.1126/science.1259329[PMID 20029940] Suggestive synergy between genetic variants in TF and HFE as risk factors for Alzheimer's disease
|Title||Genome-wide association study identifies two loci strongly affecting transferrin glycosylation.|
|Odds Ratio||0.2900 [0.25-0.33] unit decrease|
|Disease||Transferrin variant c1/c2 Alzheimer disease Atransferrinemia|
|CLNDBN||Transferrin variant c1/c2 Alzheimer disease, susceptibility to Atransferrinemia|
|CLNSRC||OMIM Allelic Variant UniProtKB (protein)|
|CLNACC||RCV000013451.23, RCV000013452.3, RCV000376325.1,|
[PMID 17357082] Identification of a novel risk locus for progressive supranuclear palsy by a pooled genomewide scan of 500,288 single-nucleotide polymorphisms.
[PMID 17601350] A genetic association analysis of cognitive ability and cognitive ageing using 325 markers for 109 genes associated with oxidative stress or cognition.
[PMID 18795173] Variants in iron metabolism genes predict higher blood lead levels in young children.
[PMID 18813964] Alzheimer's disease risk variants show association with cerebrospinal fluid amyloid beta.
[PMID 18830724] Assessment of Alzheimer's disease case-control associations using family-based methods.
[PMID 19084216] Association of genetic variants at 3q22 with nephropathy in patients with type 1 diabetes mellitus.
[PMID 19165391] Iron metabolism genes, low-level lead exposure, and QT interval.
[PMID 19673882] A novel association between a SNP in CYBRD1 and serum ferritin levels in a cohort study of HFE hereditary haemochromatosis.
[PMID 20574532] Intermediate phenotypes identify divergent pathways to Alzheimer's disease.
[PMID 20659343] HFE gene variants modify the association between maternal lead burden and infant birthweight: a prospective birth cohort study in Mexico City, Mexico.
|qualified_impact||Insufficiently evaluated not reviewed|
[PMID 23732512] Effect modification by transferrin C2 polymorphism on lead exposure, hemoglobin levels, and IQ.
[PMID 24121126] Pooled analysis of iron-related genes in Parkinson's disease: association with transferrin