Identification of a novel candidate locus for juvenile idiopathic arthritis at 14q13.2 in the Latvian population by association analysis with microsatellite markers.

To identify novel juvenile idiopathic arthritis (JIA) susceptibility loci, a 270 kb genomic region encompassing FAM177A1, KIAA0391, and PSMA6 genes was genotyped in 97 oligoarthritis (JIoA) and 50 polyarthritis (JIpA) patients and 230 individuals without autoimmune disorders by five microsatellites (MS) previously described as HSMS markers of the 14q13.2 region. Direct sequencing revealed two variable components of the (CAA)(n)(A)(m) motif in HSMS602 marker (FAM177A1 gene). Repeat (AC)(5)AT(AC)(n) of the HSMS701 (KIAA0391 gene) was variable in the Latvian population only in its downstream part. Allele (AC)(5)AT(AC)(15) of HSMS701 was found to be strongly associated with JIA (p = 4.91 x 10(-5), odds ratio [OR] = 18.87) and modestly associated with JIpA (p = 1.64 x 10(-3), OR = 15.69). Alleles (AC)(5)AT(AC)(18) of HSMS701 and (TG)(10) of HSMS702 appear to be JIA and JIoA risk factors (p = 1.09 x 10(-3), OR = 2.64 and p = 2.00 x 10(-3), OR = 7.67, respectively), but allele 168 bp of HSMS602 (p = 9.02 x 10(-4), OR = 0.35) appears to be protective. Two heterozygote genotypes (TG)(20/23) of the HSMS006 and (AC)(22/23) of the HSMS801 showed association with JIA (p < 2 x 10(-3)), but homozygote (TG)(19/19) was found to be protective (p = 5.41 x 10(-4), OR = 0.12). Our results define an additional susceptibility locus for JIA at the 14q13.2 genomic region encompassing KIAA0391 and PSMA6 genes.