Search for hand osteoarthritis susceptibility locus on chromosome 6p12.3-p12.1.
The existence of osteoarthritis susceptibility loci on chromosome 6 for individuals suffering from hip and knee osteoarthritis has been suggested. We determined whether radiographic hand osteoarthritis in a demographically homogeneous population of European origin can be linked to loci on chromosome 6p12.3-p12.1. Nine single nucleotide polymorphisms (SNPs) were genotyped in 764 individuals (members of 189 nuclear and more complex two- or three-generation families). Radiographic hand osteoarthritis was characterized by two traits: (1) the total individual osteoarthritis score (PC1-OA) and (2) the osteophytes score (PC1-OS), obtained from the principal components analysis of sums of the Kellgren and Lawrence grade and of the osteophyte grades, respectively, for 14 joints on each hand. The contribution of genetic and environmental factors and of covariates such as age and body mass index to hand osteoarthritis was evaluated by variance components analysis. The association between the studied traits and selected DNA markers was evaluated by three types of transmission disequilibrium tests. The parent-offspring and sib-sib correlations were statistically significant for all studied traits. The additive genetic effects for PC1-OA and PC1-OS were estimated to be 43% and 37.9%, respectively. Transmission disequilibrium tests consistently revealed a statistically significant association (p values ranged from 0.017 to 0.030) between SNP rs1508632 and PC1-OS. In the tested cohort the putative genetic factors are influential enough to determine interindividual differences regarding the extent of hand osteoarthritis. SNP rs1508632 lies in immediate proximity to the TINAG gene, implicating it as a possible hand osteoarthritis susceptibility gene.
Jakowlev
K
K
Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Livshits
G
G
Kalichman
L
L
Ben-Asher
E
E
Malkin
I
I
Lancet
D
D
Kobyliansky
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006225:Hand / Q000000981:diagnostic imaging*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance / Q000379:methods*; D011859:Radiography
D015395:Histocompatibility Antigens Class I; C112461:ZNRD1AS gene product, human