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From SNPedia

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
is asnp
is mentioned by
dbSNP (classic)rs143383
1000 genomesrs143383
GWAS Ctlgrs143383
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.

[PMID 19565498OA-icon.png] Functional analysis of the osteoarthritis susceptibility-associated GDF5 regulatory polymorphism


[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


[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 20870806OA-icon.png] 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.

[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

Risk Rs143383(C;C)
Alt Rs143383(C;C)
Reference Rs143383(T;T)
Significance Other
Disease Osteoarthritis of hip Fibular hypoplasia and complex brachydactyly Chondrodysplasia Acromesomelic Dysplasia Symphalangism-brachydactyly syndrome Brachydactyly
Variation info
Gene GDF5
CLNDBN Osteoarthritis of hip Fibular hypoplasia and complex brachydactyly Chondrodysplasia Acromesomelic Dysplasia Symphalangism-brachydactyly syndrome Brachydactyly
Reversed 1
HGVS NC_000020.10:g.34025983A>G
CLNSRC OMIM Allelic Variant
CLNACC RCV000008898.3, RCV000285133.1, RCV000290932.1, RCV000344695.1, RCV000350530.1, RCV000385268.1,

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

[PMID 29056119] Polymorphisms in the Growth Differentiation Factor 5 (GDF 5) Gene in Knee Osteoarthritis.

[PMID 29797005] Genetic Influence in Developmental Dysplasia of the Hip in Saudi Arabian Children Due to GDF5 Polymorphism.

[PMID 30044130] Association Between the SNP rs143383 + 104T/C in the GDF5 Gene and the Risk of Knee Osteoarthritis in a Population from Northern Mexico-A Case-Control Study.

[PMID 30186416OA-icon.png] Association between GDF5 single nucleotide polymorphism rs143383 and lumbar disc degeneration.

[PMID 32185351OA-icon.png] Genetic Association Between Growth Differentiation Factor 5 Single Nucleotide Polymorphism and Primary Knee Osteoarthritis in a Group of Egyptian Patients: A Pilot Study.