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rs143383

From SNPedia

Orientationminus
Stabilizedminus
Geno Mag Summary
(C;C) 0 normal risk for osteoarthritis
(C;T) 1.2 1.1x increased risk for osteoarthritis
(T;T) 1.8 1.3x increased risk for osteoarthritis
ReferenceGRCh38 38.1/141
Chromosome20
Position35438203
GeneGDF5
is asnp
is mentioned by
dbSNPrs143383
ebirs143383
HLIrs143383
Exacrs143383
Varsomers143383
Maprs143383
PheGenIrs143383
hapmaprs143383
1000 genomesrs143383
hgdprs143383
ensemblrs143383
gopubmedrs143383
geneviewrs143383
scholarrs143383
googlers143383
pharmgkbrs143383
gwascentralrs143383
openSNPrs143383
23andMers143383
23andMe allrs143383
SNP Nexus

SNPshotrs143383
SNPdbers143383
MSV3drs143383
GWAS Ctlgrs143383
GMAF0.4646
Max Magnitude1.8
? (C;C) (C;T) (T;T) 28

This SNP is associated with osteoarthritis (OA). It is located in the five prime untranslated region (5′UTR) of the gene encoding growth differentiation factor 5 (GDF5), a chondrogenic protein active from the embryonic stage onwards. GDF5 is also known as cartilage-derived morphogenetic protein 1 or BMP14.

The risk allele T (+ 104T/C;rs143383) causes reduction of the GDF5 promoter sequence activity. Reduction of GDF5 in human cartilage of patients with OA by up to 27% has been observed [1]. This effect is influenced by a second SNP ( rs143384 , C/T ) in the same area. The C alleles of both SNPs form CpG dinucleotides. Demethylation of both SNP's increases GDF5 expression.[2] [PMID 21642387] "Expression of the osteoarthritis-associated gene GDF5 is modulated epigenetically by DNA methylation." Thus the authors conclude that epigenetic manipulation offers options in developing therapies for OA.

[PMID 17384641] rs143383 showed significant association with hip osteoarthritis in two independent Japanese populations. It also showed association with knee osteoarthritis in Japanese and Chinese populations.

[PMID 17676627] is *not* a risk factor for osteoarthritis in Greek Caucasians

A subsequent study showed that the same risk allele, rs143383(T), was (somewhat) associated with osteoarthritis in European populations. The odds ratio was 1.10 for the allele, 1.28 for carrier status (p=0.03, p=0.004, respectively). The (T) allele appears to make less GDF5 protein, which eventually renders an individual somewhat more susceptible to osteoarthritis.[PMID 17616513]

A meta-analysis combining data from 11,000+ individuals as well as both European and Asian populations found strong evidence (p < 0.0004) confirming increased risk for osteoarthritis from the rs143383(T) allele. The best model is a dominant one, and the odds ratio reported is 1.21 in general and 1.48 for the dominant model.[PMID 18299287]

Another meta-analysis of 14 studies concluded that rs143383 did indeed show significant association with osteoarthritis, at least for knee osteoarthritis, and probably for hand and hip (but to a lesser degree). The effect size wasn't large, though (odds ratio 1.15, CI: 1.09-1.22, p = 9.4 x 10e-7).[PMID 19479880OA-icon.png]

A haplotype of rs143383 and rs6060369 can be defined, which also links osteoarthritis to height since rs6060369 was linked to height in a study ultimately involving over 28,000 individuals.[PMID 18193045OA-icon.png]

The Medpage article on this finding notes that rs143383 was previously shown to be associated with increased risk for osteoarthritis and in this recent study [PMID 18193045OA-icon.png] it was significantly associated with shorter height in the initial scans, at p=2.70x10e-5.

Note that the authors of [PMID 18193045OA-icon.png] refer to rs143383 in the opposite orientation compared to it's entry in dbSNP.

[PMID 18947434OA-icon.png] A study of 338 Han Chinese children affected by congenital dysplasia of the hip revealed that rs143383(T) alleles conferred a 1.4x increased risk for the disorder, particularly in females (odds ratio 1.43, CI: 1.11 - 1.85, p = 0.0078).

[PMID 19029166] A study of 6,365 elderly Caucasian men and women observed significant association between rs143383 and osteoarthritis, height, bone size and fracture risk in women.

Neighborrs28936397
Distance791


[PMID 19565498] Functional analysis of the osteoarthritis susceptibility-associated GDF5 regulatory polymorphism

OMIM612228
DescSTATURE QUANTITATIVE TRAIT LOCUS 14; STQTL14
Variant
Relatedalso
OMIM601146
DescGROWTH/DIFFERENTIATION FACTOR 5; GDF5
Variant
Relatedalso



[PMID 20499385] Different risk factors are involved in clinically severe large joint osteoarthritis according to the presence of hand interphalangeal nodes

[PMID 20633687] Evidence of association between GDF5 polymorphisms and congenital dislocation of the hip in a Caucasian population

[PMID 21128259] GDF5 SNP rs143383 is associated with lumbar disc disease in northern European women

OMIM601146
Desc
Variant0015
Relatedalso
[PMID 21542882OA-icon.png] Knee osteoarthritis, lumbar-disc degeneration and developmental dysplasia of the hip - an emerging genetic overlap


[PMID 22284607] Genetic association analysis of GDF5 and ADAM12 for knee osteoarthritis.


[PMID 18245884] [Genomic approaches to bone and joint diseases. Current status of genetic study of osteoarthritis].


[PMID 18471798OA-icon.png] Genome-wide association scan identifies a prostaglandin-endoperoxide synthase 2 variant involved in risk of knee osteoarthritis.


[PMID 19054821] Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations.


[PMID 19343178OA-icon.png] Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size.


[PMID 20237151] Field synopsis and synthesis of genetic association studies in osteoarthritis: the CUMAGAS-OSTEO information system.


[PMID 20360039] Components of the transforming growth factor-beta family and the pathogenesis of human Achilles tendon pathology--a genetic association study.


[PMID 20870806] The GDF5 rs143383 polymorphism is associated with osteoarthritis of the knee with genome-wide statistical significance.


[PMID 21154330] [Association of genetic and mechanical factors with age of onset of knee osteoarthritis].


[PMID 21281725] Deep sequencing of GDF5 reveals the absence of rare variants at this important osteoarthritis susceptibility locus.


[PMID 21360499OA-icon.png] GDF5 single-nucleotide polymorphism rs143383 is associated with lumbar disc degeneration in Northern European women.


[PMID 22615457OA-icon.png] Genetic contribution to radiographic severity in osteoarthritis of the knee.


GET Evidence
rs143383
aa_change
aa_change_short
impact pharmacogenetic
qualified_impact Insufficiently evaluated pharmacogenetic
overall_frequency 0.565574
summary



[PMID 23090674] The GDF5 Gene and Anterior Cruciate Ligament Rupture


[PMID 23825960OA-icon.png] The Identification of Trans-acting Factors That Regulate the Expression of GDF5 via the Osteoarthritis Susceptibility SNP rs143383


[PMID 24003854] The genetics of common degenerative skeletal disorders: osteoarthritis and degenerative disc disease


[PMID 24105021OA-icon.png] A SNP in the 5'UTR of GDF5 is associated with susceptibility to symptomatic lumbar disc herniation in the Chinese Han population


[PMID 24227118] The GDF5 SNP is Associated with Meniscus Injury and Function Recovery in Male Chinese Soldiers


[PMID 22929025OA-icon.png] A rare variant in the osteoarthritis-associated locus GDF5 is functional and reveals a site that can be manipulated to modulate GDF5 expression.


[PMID 22956599OA-icon.png] Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data.


[PMID 23357225] Association study of candidate genes for the progression of hand osteoarthritis.


[PMID 24861163OA-icon.png] CpG methylation regulates allelic expression of GDF5 by modulating binding of SP1 and SP3 repressor proteins to the osteoarthritis susceptibility SNP rs143383


ClinVar
Risk rs143383(C;C)
Alt rs143383(C;C)
Reference rs143383(T;T)
Significance Other
Disease Osteoarthritis of hip
Variation info
Gene GDF5
CLNDBN Osteoarthritis of hip
Reversed 1
HGVS NC_000020.10:g.34025983A>G
CLNSRC OMIM Allelic Variant
CLNACC RCV000008898.3,



[PMID 25894512] A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand