{{Rsnum
|rsid=143383
|Gene=GDF5
|Chromosome=20
|position=35438203
|Orientation=minus
|GMAF=0.4646
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 10.8 | 43.1 | 46.2
| HCB | 4.7 | 34.9 | 60.5
| JPT | 2.3 | 44.2 | 53.5
| YRI | 100.0 | 0.0 | 0.0
| ASW | 0.0 | 0.0 | 0.0
| CHB | 4.7 | 34.9 | 60.5
| CHD | 0.0 | 0.0 | 0.0
| GIH | 0.0 | 0.0 | 0.0
| LWK | 0.0 | 0.0 | 0.0
| MEX | 0.0 | 0.0 | 0.0
| MKK | 0.0 | 0.0 | 0.0
| TSI | 0.0 | 0.0 | 0.0
| HapMapRevision=28
}}
This SNP is associated with [[osteoarthritis]] (OA). It is located in the ''five prime untranslated region'' ([http://en.wikipedia.org/wiki/Five_prime_untranslated_region| '''5′UTR''']) of the gene encoding ''growth differentiation factor 5'' ([http://en.wikipedia.org/wiki/GDF5| '''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 [http://ora.ox.ac.uk/objects/uuid:0762a66d-2035-4a96-b16b-2a81686b1be8]. 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.[http://hmg.oxfordjournals.org/content/20/17/3450.long] {{PMID Auto
|PMID=21642387
|Title="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|19479880}}

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|18193045|OA=1
}}

The [http://www.medpagetoday.com/PublicHealthPolicy/Genetics/tb/7961 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|18193045|OA=1
}} it was significantly associated with shorter height in the initial scans, at p=2.70x10e-5.

Note that the authors of {{PMID|18193045|OA=1
}} refer to [[rs143383]] in the opposite orientation compared to it's entry in dbSNP. 

{{PMID|18947434|OA=1
}} 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.

{{ neighbor
| rsid = 28936397
| distance = 791
}}

{{PMID Auto
|PMID=19565498
|Title=Functional analysis of the osteoarthritis susceptibility-associated GDF5 regulatory polymorphism
}}

{{omim
|desc=STATURE QUANTITATIVE TRAIT LOCUS 14; STQTL14
|id=612228
|rsnum=143383
}}

{{omim
|id=601146
|desc=GROWTH/DIFFERENTIATION FACTOR 5; GDF5
|rsnum=143383
}}

{{PharmGKB
|RSID=rs143383
|Name_s=GDF5: +104T/C
|Gene_s=GDF5
|Feature=
|Evidence=PubMed ID:17384641; PubMed ID:17616513; PubMed ID:18299287
|Annotation=This SNP in the 5' UTR of GDF5 showed significant association with hip osteoarthritis in two independent Japanese populations. Another study confirmed the association of the SNP with osteoarthritis susceptibility in Europeans. The associated T-allele showed up to a 27% reduction in expression relative to the C-allele.
|Drugs=
|Drug Classes=
|Diseases=Osteoarthritis, Hip
|Curation Level=Curated
|PharmGKB Accession ID=PA161925628
}}

{{PMID Auto
|PMID=20499385
|Title=Different risk factors are involved in clinically severe large joint osteoarthritis according to the presence of hand interphalangeal nodes
}}
{{PMID Auto
|PMID=20633687
|Title=Evidence of association between GDF5 polymorphisms and congenital dislocation of the hip in a Caucasian population
}}
{{PMID Auto
|PMID=21128259
|Title=GDF5 SNP rs143383 is associated with lumbar disc disease in northern European women
}}

{{omim
|id=601146
|rsnum=143383
|variant=0015
}}

{{PMID Auto
|PMID=21542882
|Title=Knee osteoarthritis, lumbar-disc degeneration and developmental dysplasia of the hip - an emerging genetic overlap
|OA=1
}}

{{PMID Auto
|PMID=22284607
|Title=Genetic association analysis of GDF5 and ADAM12 for knee osteoarthritis.
}}

{{PMID Auto
|PMID=18245884
|Title=[Genomic approaches to bone and joint diseases. Current status of genetic study of osteoarthritis].
}}

{{PMID Auto
|PMID=18471798
|Title=Genome-wide association scan identifies a prostaglandin-endoperoxide synthase 2 variant involved in risk of knee osteoarthritis.
|OA=1
}}

{{PMID Auto
|PMID=19054821
|Title=Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations.
}}

{{PMID Auto
|PMID=19343178
|Title=Meta-analysis of genome-wide scans for human adult stature identifies novel Loci and associations with measures of skeletal frame size.
|OA=1
}}

{{PMID Auto
|PMID=20237151
|Title=Field synopsis and synthesis of genetic association studies in osteoarthritis: the CUMAGAS-OSTEO information system.
}}

{{PMID Auto
|PMID=20360039
|Title=Components of the transforming growth factor-beta family and the pathogenesis of human Achilles tendon pathology--a genetic association study.
}}

{{PMID Auto
|PMID=20870806
|Title=The GDF5 rs143383 polymorphism is associated with osteoarthritis of the knee with genome-wide statistical significance.
}}

{{PMID Auto
|PMID=21154330
|Title=[Association of genetic and mechanical factors with age of onset of knee osteoarthritis].
}}

{{PMID Auto
|PMID=21281725
|Title=Deep sequencing of GDF5 reveals the absence of rare variants at this important osteoarthritis susceptibility locus.
}}

{{PMID Auto
|PMID=21360499
|Title=GDF5 single-nucleotide polymorphism rs143383 is associated with lumbar disc degeneration in Northern European women.
|OA=1
}}

{{PMID Auto
|PMID=22615457
|Title=Genetic contribution to radiographic severity in osteoarthritis of the knee.
|OA=1
}}

{{GET Evidence
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs143383
|overall_frequency_n=69
|overall_frequency_d=122
|overall_frequency=0.565574
|n_genomes=36
|n_genomes_annotated=0
|n_haplomes=57
|n_articles=0
|n_articles_annotated=0
|in_pharmgkb=Y
|autoscore=1
|webscore=N
}}

{{PMID Auto
|PMID=23090674
|Title=The GDF5 Gene and Anterior Cruciate Ligament Rupture
}}

{{PMID Auto
|PMID=23825960
|Title=The Identification of Trans-acting Factors That Regulate the Expression of GDF5 via the Osteoarthritis Susceptibility SNP rs143383
|OA=1
}}

{{PMID Auto
|PMID=24003854
|Title=The genetics of common degenerative skeletal disorders: osteoarthritis and degenerative disc disease
}}

{{PMID Auto
|PMID=24105021
|Title=A SNP in the 5'UTR of GDF5 is associated with susceptibility to symptomatic lumbar disc herniation in the Chinese Han population
}}

{{PMID Auto
|PMID=24227118
|Title=The GDF5 SNP is Associated with Meniscus Injury and Function Recovery in Male Chinese Soldiers
}}

{{PMID Auto
|PMID=22929025
|Title=A rare variant in the osteoarthritis-associated locus GDF5 is functional and reveals a site that can be manipulated to modulate GDF5 expression.
|OA=1
}}

{{PMID Auto
|PMID=22956599
|Title=Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data.
|OA=1
}}

{{PMID Auto
|PMID=23357225
|Title=Association study of candidate genes for the progression of hand osteoarthritis.
}}

{{PMID Auto
|PMID=24861163
|Title=CpG methylation regulates allelic expression of GDF5 by modulating binding of SP1 and SP3 repressor proteins to the osteoarthritis susceptibility SNP rs143383
}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}