Variant "XYLT2:rs6504649"
Search results: 2 records
Variant information
Gene:
XYLT2 
Variant:
XYLT2:rs6504649 
Alias:
XYLT2:c.2402C>G 
dbSNP ID:
rs6504649  
GWAS trait:
no data 
Modifier statisitcs
Record:
2 
Disorder:
1 
Reference:
1 
Effect type:
Expressivity(2)  
Modifier effect:
Higher organ involvement(1) ,Risk factor(1)  
Details：
  • Target disease:
    Pseudoxanthoma Elasticum (DOID_2738)
    Effect type:
    Expressivity 
    Modifier effect:
    Higher organ involvement 
    Evidence:
    P=0.02 
    Effect:
    c.166G>A, c.1569C>T, and c.2402C>G in the XYLT-II gene were found to be more frequent in patients with higher organ involvement (P=0.04, P=0.01, and P=0.02, respectively).
    Alias in reference:
    XYLT2:c.2402C>G
    Reference:
    PMID16571645
    Title:
    Polymorphisms in the xylosyltransferase genes cause higher serum XT-I activity in patients with pseudoxanthoma elasticum (PXE) and are involved in a severe disease course.
    Species studied:
    Human
    Abstract:
    BACKGROUND:Pseudoxanthoma elasticum (PXE) is a heritable connective tissue disorder caused by mutations in the ABCC6 gene. Fragmentation of elastic fibres and deposition of proteoglycans result in a highly variable clinical picture. The altered proteoglycan metabolism suggests that enzymes from this pathway function as genetic co-factors in the severity of PXE. Therefore, we propose the XYLT genes encoding xylosyltransferase I (XT-I) as the chain-initiating enzyme in the biosynthesis of proteoglycans and the highly homologous XT-II as potential candidate genes. METHODS:We screened all XYLT exons in 65 German PXE patients using denaturing high performance liquid chromatography and analysed the influence of the variations on clinical characteristics. RESULTS:We identified 22 variations in the XYLT genes. The missense variation p.A115S (XT-I) is associated with higher serum XT activity (p = 0.005). The amino acid substitution p.T801R (XT-II; c.2402C>G) occurs with significantly higher frequency in patients under 30 years of age at diagnosis (43% v 26%; p = 0.04); all PXE patients with this variation suffer from skin lesions compared to only 75% of the wild type patients (p = 0.002). c.166G>A, c.1569C>T, and c.2402C>G in the XYLT-II gene were found to be more frequent in patients with higher organ involvement (p = 0.04, p = 0.01, and p = 0.02, respectively). CONCLUSIONS:Here we show for the first time that variations in the XYLT-II gene are genetic co-factors in the severity of PXE. Furthermore, the higher XT activity in patients with the exchange p.A115S (XT-I) indicates that this polymorphism is a potential marker for increased remodelling of the extracellular matrix.
  • Target disease:
    Pseudoxanthoma Elasticum (DOID_2738)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    P=0.04 
    Effect:
    The amino acid substitution p.T801R (XT-II; c.2402C>G) occurs with significantly higher frequency in patients under 30 years of age at diagnosis (43% v 26%; P=0.04); all PXE patients with this variation suffer from skin lesions
    Alias in reference:
    XYLT2:rs6504649
    Reference:
    PMID16571645
    Title:
    Polymorphisms in the xylosyltransferase genes cause higher serum XT-I activity in patients with pseudoxanthoma elasticum (PXE) and are involved in a severe disease course.
    Species studied:
    Human
    Abstract:
    BACKGROUND:Pseudoxanthoma elasticum (PXE) is a heritable connective tissue disorder caused by mutations in the ABCC6 gene. Fragmentation of elastic fibres and deposition of proteoglycans result in a highly variable clinical picture. The altered proteoglycan metabolism suggests that enzymes from this pathway function as genetic co-factors in the severity of PXE. Therefore, we propose the XYLT genes encoding xylosyltransferase I (XT-I) as the chain-initiating enzyme in the biosynthesis of proteoglycans and the highly homologous XT-II as potential candidate genes. METHODS:We screened all XYLT exons in 65 German PXE patients using denaturing high performance liquid chromatography and analysed the influence of the variations on clinical characteristics. RESULTS:We identified 22 variations in the XYLT genes. The missense variation p.A115S (XT-I) is associated with higher serum XT activity (p = 0.005). The amino acid substitution p.T801R (XT-II; c.2402C>G) occurs with significantly higher frequency in patients under 30 years of age at diagnosis (43% v 26%; p = 0.04); all PXE patients with this variation suffer from skin lesions compared to only 75% of the wild type patients (p = 0.002). c.166G>A, c.1569C>T, and c.2402C>G in the XYLT-II gene were found to be more frequent in patients with higher organ involvement (p = 0.04, p = 0.01, and p = 0.02, respectively). CONCLUSIONS:Here we show for the first time that variations in the XYLT-II gene are genetic co-factors in the severity of PXE. Furthermore, the higher XT activity in patients with the exchange p.A115S (XT-I) indicates that this polymorphism is a potential marker for increased remodelling of the extracellular matrix.