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rs10044254

From SNPedia

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Make rs10044254(A;A)
Make rs10044254(A;G)
Make rs10044254(G;G)
ReferenceGRCh38 38.1/141
Chromosome5
Position15783487
GeneFBXL7
is asnp
is mentioned by
dbSNPrs10044254
ebirs10044254
HLIrs10044254
Exacrs10044254
Varsomers10044254
Maprs10044254
PheGenIrs10044254
hapmaprs10044254
1000 genomesrs10044254
hgdprs10044254
ensemblrs10044254
gopubmedrs10044254
geneviewrs10044254
scholarrs10044254
googlers10044254
pharmgkbrs10044254
gwascentralrs10044254
openSNPrs10044254
23andMers10044254
23andMe allrs10044254
SNP Nexus

SNPshotrs10044254
SNPdbers10044254
MSV3drs10044254
GWAS Ctlgrs10044254
Max Magnitude
? (A;A) (A;G) (G;G) 28
This SNP is in the intronic region of the F-box and leucine-rich repeat protein 7 (FBXL7), and it is associated with response to inhaled corticosteroid (ICS) treatment in children with asthma. In an ICS treatment trial for children [PMID 24486069OA-icon.png], rs10044254 was associated with downregulation of FBXL7 expression, a gene encoding one of four subunits of the SKP1-cullin-F-box ubiquitin protein ligase complex. In the same study, in two independent cohorts, children with at least one copy of the reference allele (A) had better symptomatic response to inhaled corticosteroids (ICSs), the main treatment for asthma, when compared to children homozygous for the variant allele (G), whose symptoms worsened during the treatment.

The first cohort group, composed of 124 white children in an ICS treatment trial (average age 8.9 years), relied on daily self-reported (with parents’ participation) asthma symptoms ranked from 0 to 3. They tested 440,862 SNPs and then followed up on the 3 most significantly associated SNPs in a second cohort, made up of three independent populations: one of children (average age 10.4) and two of adults (33-34 years old on average). In total, there were 421 subjects, which is a very small sample size. All children were treated and followed up over the course of 8 weeks. The combined p-value for rs10044254 was 9.12 x 10-8. Another SNP, rs2388639, had a p-value of 8.56 x 10-9. These significant associations were not replicated in the adult cohorts, suggesting the associations only apply to children. Additionally, the effect size (the reduction in asthma symptoms rank) was small for both groups and the standard deviation really high, so it is not clear whether this result is clinically relevant. Adding the fact that the sample size was really small makes the evidence even weaker.

Expression profiles of FBXL7 in response to dexamethasone (an ICS) stimulation was measured in B-cell lines derived from 70 patients in the first cohort. The rs10044254 GG genotype corresponded to lower levels of FBXL7 expression, although this effect was incredibly small and these results are highly questionable. Even if this SNP is actually an eQTL of FBXL7, its effect is very weak. Furthermore, the possible interactions of this protein with dexamethasone are not known, although some theories are provided by the authors.

Reference: Park, et al. (2014). Genetic predictors associated with improvement of asthma symptoms in response to inhaled corticosteroids. J Allergy Clin Immunol, 133(3): 664-669. [PMID 24486069OA-icon.png]