Rs143383

This SNP is associated with osteoarthritis (OA). It is located in the five prime untranslated region (| 5&#8242;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. 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. Thus the authors conclude that epigenetic manipulation offers options in developing therapies for OA.

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

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.

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.

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).

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.

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 it was significantly associated with shorter height in the initial scans, at p=2.70x10e-5.

Note that the authors of refer to rs143383 in the opposite orientation compared to it's entry in dbSNP.

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).

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.