Radiographic osteoarthritis at three joint sites and FRZB, LRP5, and LRP6 polymorphisms in two population-based cohorts

J. M. Kerkhof; A. G. Uitterlinden; A. M. Valdes; D. J. Hart; F. Rivadeneira; M. Jhamai; A. Hofman; H. A. P. Pols; S. M. A. Bierma-Zeinstra; T. D. Spector; J. B. van Meurs

doi:10.1016/j.joca.2008.02.007

Radiographic osteoarthritis at three joint sites and FRZB, LRP5, and LRP6 polymorphisms in two population-based cohorts

J. M. Kerkhof, A. G. Uitterlinden, A. M. Valdes, D. J. Hart, F. Rivadeneira, M. Jhamai, A. Hofman, H. A. P. Pols, S. M. A. Bierma-Zeinstra, T. D. Spector, J. B. van Meurs

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Abstract

Objective: To examine the association of genetic variation in key players in the Wnt signaling pathway with aspects of osteoarthritis (OA) in two population-based cohort studies: the Rotterdam Study and the Chingford Study. Methods: Radiographic OA (ROA) was defined as a Kellgren/Lawrence score (K/L) score >= 2 for the knee and hip. Total hip replacement (THR) was scored. Hand OA was defined as presence of ROA (K/L >= 2) in two out of three hand joint groups [distal interphalangeal (DIPs), proximal interphalangeal (PIPs), first carpometacarpal (CMC1)/trapezio-scaphoid joint (TS)] of each hand. The concentration of urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II) was standardized to the total urine creatinine. Genotypes for the amino acid variants, Arg200Trp and Arg324Gly of Frizzled-Related protein gene (FRZB), Ala1330Val of Low-density lipoprotein receptor-related protein 5 (LRP5) and Ile1062Val of Low-density lipoprotein receptor-related protein 6 (LRP6), were obtained using the Tagman allelic discrimination assay. A meta-analysis was performed for the FRZB Arg324Gly polymorphism and hip- and knee-OA using RevMan version 4.3. Results: No consistent associations were observed between the FRZB, LRP5 and LRP6 amino acid variants and radiographic hip-, knee-, or hand-OA or THR, in either study population, While power was limited for most studies to date, a meta-analysis of all published studies regarding the FRZB Arg324Gly polymorphism was performed for hip- and knee-OA seperately. This showed no significant associations between the Gly324 allele and risk for hip- or knee OA, although there was large heterogeneity between studies for hip OA in females. Conclusion: No association was seen between FRZB, LRP5 and LRP6 variants with radiographic osteoarthritic outcomes in two population-based cohorts. In future studies, increased power and standardization of OA-phenotypes are highly recommended for replication studies and to allow meta-analysis. (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	1141 - 1149
Number of pages	9
Journal	Osteoarthritis and Cartilage
Volume	16
Issue number	10
DOIs	https://doi.org/10.1016/j.joca.2008.02.007
Publication status	Published - Oct 2008

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Kerkhof, J. M., Uitterlinden, A. G., Valdes, A. M., Hart, D. J., Rivadeneira, F., Jhamai, M., Hofman, A., Pols, H. A. P., Bierma-Zeinstra, S. M. A., Spector, T. D., & van Meurs, J. B. (2008). Radiographic osteoarthritis at three joint sites and FRZB, LRP5, and LRP6 polymorphisms in two population-based cohorts. Osteoarthritis and Cartilage, 16(10), 1141 - 1149. https://doi.org/10.1016/j.joca.2008.02.007

@article{34e6326af8b648fb83f4a2242fea28de,

title = "Radiographic osteoarthritis at three joint sites and FRZB, LRP5, and LRP6 polymorphisms in two population-based cohorts",

abstract = "Objective: To examine the association of genetic variation in key players in the Wnt signaling pathway with aspects of osteoarthritis (OA) in two population-based cohort studies: the Rotterdam Study and the Chingford Study. Methods: Radiographic OA (ROA) was defined as a Kellgren/Lawrence score (K/L) score >= 2 for the knee and hip. Total hip replacement (THR) was scored. Hand OA was defined as presence of ROA (K/L >= 2) in two out of three hand joint groups [distal interphalangeal (DIPs), proximal interphalangeal (PIPs), first carpometacarpal (CMC1)/trapezio-scaphoid joint (TS)] of each hand. The concentration of urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II) was standardized to the total urine creatinine. Genotypes for the amino acid variants, Arg200Trp and Arg324Gly of Frizzled-Related protein gene (FRZB), Ala1330Val of Low-density lipoprotein receptor-related protein 5 (LRP5) and Ile1062Val of Low-density lipoprotein receptor-related protein 6 (LRP6), were obtained using the Tagman allelic discrimination assay. A meta-analysis was performed for the FRZB Arg324Gly polymorphism and hip- and knee-OA using RevMan version 4.3. Results: No consistent associations were observed between the FRZB, LRP5 and LRP6 amino acid variants and radiographic hip-, knee-, or hand-OA or THR, in either study population, While power was limited for most studies to date, a meta-analysis of all published studies regarding the FRZB Arg324Gly polymorphism was performed for hip- and knee-OA seperately. This showed no significant associations between the Gly324 allele and risk for hip- or knee OA, although there was large heterogeneity between studies for hip OA in females. Conclusion: No association was seen between FRZB, LRP5 and LRP6 variants with radiographic osteoarthritic outcomes in two population-based cohorts. In future studies, increased power and standardization of OA-phenotypes are highly recommended for replication studies and to allow meta-analysis. (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.",

author = "Kerkhof, {J. M.} and Uitterlinden, {A. G.} and Valdes, {A. M.} and Hart, {D. J.} and F. Rivadeneira and M. Jhamai and A. Hofman and Pols, {H. A. P.} and Bierma-Zeinstra, {S. M. A.} and Spector, {T. D.} and {van Meurs}, {J. B.}",

year = "2008",

month = oct,

doi = "10.1016/j.joca.2008.02.007",

language = "English",

volume = "16",

pages = "1141 -- 1149",

journal = "Osteoarthritis and Cartilage",

publisher = "Elsevier",

number = "10",

}

Kerkhof, JM, Uitterlinden, AG, Valdes, AM, Hart, DJ, Rivadeneira, F, Jhamai, M, Hofman, A, Pols, HAP, Bierma-Zeinstra, SMA, Spector, TD & van Meurs, JB 2008, 'Radiographic osteoarthritis at three joint sites and FRZB, LRP5, and LRP6 polymorphisms in two population-based cohorts', Osteoarthritis and Cartilage, vol. 16, no. 10, pp. 1141 - 1149. https://doi.org/10.1016/j.joca.2008.02.007

TY - JOUR

T1 - Radiographic osteoarthritis at three joint sites and FRZB, LRP5, and LRP6 polymorphisms in two population-based cohorts

AU - Kerkhof, J. M.

AU - Uitterlinden, A. G.

AU - Valdes, A. M.

AU - Hart, D. J.

AU - Rivadeneira, F.

AU - Jhamai, M.

AU - Hofman, A.

AU - Pols, H. A. P.

AU - Bierma-Zeinstra, S. M. A.

AU - Spector, T. D.

AU - van Meurs, J. B.

PY - 2008/10

Y1 - 2008/10

N2 - Objective: To examine the association of genetic variation in key players in the Wnt signaling pathway with aspects of osteoarthritis (OA) in two population-based cohort studies: the Rotterdam Study and the Chingford Study. Methods: Radiographic OA (ROA) was defined as a Kellgren/Lawrence score (K/L) score >= 2 for the knee and hip. Total hip replacement (THR) was scored. Hand OA was defined as presence of ROA (K/L >= 2) in two out of three hand joint groups [distal interphalangeal (DIPs), proximal interphalangeal (PIPs), first carpometacarpal (CMC1)/trapezio-scaphoid joint (TS)] of each hand. The concentration of urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II) was standardized to the total urine creatinine. Genotypes for the amino acid variants, Arg200Trp and Arg324Gly of Frizzled-Related protein gene (FRZB), Ala1330Val of Low-density lipoprotein receptor-related protein 5 (LRP5) and Ile1062Val of Low-density lipoprotein receptor-related protein 6 (LRP6), were obtained using the Tagman allelic discrimination assay. A meta-analysis was performed for the FRZB Arg324Gly polymorphism and hip- and knee-OA using RevMan version 4.3. Results: No consistent associations were observed between the FRZB, LRP5 and LRP6 amino acid variants and radiographic hip-, knee-, or hand-OA or THR, in either study population, While power was limited for most studies to date, a meta-analysis of all published studies regarding the FRZB Arg324Gly polymorphism was performed for hip- and knee-OA seperately. This showed no significant associations between the Gly324 allele and risk for hip- or knee OA, although there was large heterogeneity between studies for hip OA in females. Conclusion: No association was seen between FRZB, LRP5 and LRP6 variants with radiographic osteoarthritic outcomes in two population-based cohorts. In future studies, increased power and standardization of OA-phenotypes are highly recommended for replication studies and to allow meta-analysis. (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

AB - Objective: To examine the association of genetic variation in key players in the Wnt signaling pathway with aspects of osteoarthritis (OA) in two population-based cohort studies: the Rotterdam Study and the Chingford Study. Methods: Radiographic OA (ROA) was defined as a Kellgren/Lawrence score (K/L) score >= 2 for the knee and hip. Total hip replacement (THR) was scored. Hand OA was defined as presence of ROA (K/L >= 2) in two out of three hand joint groups [distal interphalangeal (DIPs), proximal interphalangeal (PIPs), first carpometacarpal (CMC1)/trapezio-scaphoid joint (TS)] of each hand. The concentration of urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II) was standardized to the total urine creatinine. Genotypes for the amino acid variants, Arg200Trp and Arg324Gly of Frizzled-Related protein gene (FRZB), Ala1330Val of Low-density lipoprotein receptor-related protein 5 (LRP5) and Ile1062Val of Low-density lipoprotein receptor-related protein 6 (LRP6), were obtained using the Tagman allelic discrimination assay. A meta-analysis was performed for the FRZB Arg324Gly polymorphism and hip- and knee-OA using RevMan version 4.3. Results: No consistent associations were observed between the FRZB, LRP5 and LRP6 amino acid variants and radiographic hip-, knee-, or hand-OA or THR, in either study population, While power was limited for most studies to date, a meta-analysis of all published studies regarding the FRZB Arg324Gly polymorphism was performed for hip- and knee-OA seperately. This showed no significant associations between the Gly324 allele and risk for hip- or knee OA, although there was large heterogeneity between studies for hip OA in females. Conclusion: No association was seen between FRZB, LRP5 and LRP6 variants with radiographic osteoarthritic outcomes in two population-based cohorts. In future studies, increased power and standardization of OA-phenotypes are highly recommended for replication studies and to allow meta-analysis. (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

U2 - 10.1016/j.joca.2008.02.007

DO - 10.1016/j.joca.2008.02.007

M3 - Article

VL - 16

SP - 1141

EP - 1149

JO - Osteoarthritis and Cartilage

JF - Osteoarthritis and Cartilage

IS - 10

ER -

Radiographic osteoarthritis at three joint sites and FRZB, LRP5, and LRP6 polymorphisms in two population-based cohorts

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