**11. Calmodulin 1 (***CALM1***) gene**

Rhyner et al. [126] found that the *CALM1* gene contains six exons spread over about 10 kb of genomic DNA. The exon-intron structure was identical to that of *CALM3*. A cluster of transcription-start sites was identified 200 bp upstream of the ATG translation-start codon, and several putative regulatory elements were found in the 5′ flanking region, as well as in intron 1. A short CAG trinucleotide repeat region was identified in the 5-prime untranslated region of the gene. Motoani *et al*. [127] identified susceptibility genes for Osteoarthritis in a large-scale case-control association study using gene-based single-nucleotide polymorphism (SNPs) in a Japanese population. In two independent case-control populations, they found a significant association (p = 9.8 x10−7) between hip osteoarthritis and an SNP (IVS 3–293 C>T) located in intron 3 of the calmodulin (Cam) 1 gene (*CALM-1). CALM 1* was expressed in cultured chondrocytes, and articular cartilage and its expression were increased in Osteoarthritis. Subsequent linkage – disequilibrium mapping identified five SNPs showing significant equivalent to IVS 3–293 C>T. One of these (−16 C>T) is located in the core promoter region of *CALM 1*. Functional analysis indicated that the susceptibility – 16 T allele decreases *CALM 1* transcription in-vitro and in-vivo. Inhibition of CAM in chondrogenic cells reduced the expression of the major cartilage matrix genes *col 2a1* and *Agc 1*. These results suggested that the transcriptional level of *CALM-1* was associated with susceptibility for hip osteoarthritis through modulation of chondrogenic activity. Their findings revealed that the *CALM-1* mediated signaling pathway is chondrocytes as a novel potential target for the treatment of Osteoarthritis. Loughlin *et al*. [128] studied in a Caucasian population using a cohort of 1672 individuals and concluded that *CALM-1* core promoter polymorphism is not a risk factor for Osteoarthritis.
