- Email: [email protected]
Validation of the TAGAP rs212389 polymorphism in rheumatoid arthritis susceptibility
Letters to the editor / Joint Bone Spine 38 (2013) 541–555
543
Table 1 Rheumatoid arthritis (RA) and control subjects’ characteristics.
References [1] Shadgan B, Menon M, O’Brien PJ, et al. Diagnostic techniques in acute compartment syndrome of the leg. J Orthop Trauma 2008;22:581–7. [2] Mahmud W, Lightfoot JD, Shekhar A. Rhabdomyolysis and compartment syndrome with coadministration of risperidone and simvastatin. J Psychopharmacol 2004;18:432–4. [3] Schneider JM, Roger DJ, Uhl RL. Bilateral forearm compartment syndromes resulting from neuroleptic malignant syndrome. J Hand Surg [Am] 1996;21:287–9. [4] Murdock M, Murdoch MM. Compartment syndrome: a review of the literature. Clin Pediatr Med Surg 2012;29:301–10. [5] Masquelet AC. Traitement chirurgical du syndrome des loges et du syndrome de Volkmann. EMC-Techniques chirurgicales-Orthopédie-Traumatologie 2001:44–078.
Goulven Rochcongar a,∗ Gwenola Maigné b Vincent Pineau a Christophe Hulet a a Department of Orthopaedic and Traumatology, CHU de Caen, avenue Côte-de-Nacre, 14003 Caen cedex 9, France b Department of Internal Medicine, CHU de Caen, avenue Côte-de-Nacre, 14003 Caen cedex 9, France ∗ Corresponding
author. Tel.: +33 06 48 13 24 16; fax: +33 02 31 06 48 90. E-mail addresses: [email protected], [email protected] (G. Rochcongar) Accepted 11 January 2013 Available online 6 April 2013
doi:10.1016/j.jbspin.2013.02.006
Validation of the TAGAP rs212389 polymorphism in rheumatoid arthritis susceptibility
a r t i c l e
i n f o
Keywords: Rheumatoid arthritis Polymorphism TAGAP
Rheumatoid arthritis (RA) is a chronic inflammatory disorder in which both genetic and environmental factors have been implicated [1]. T-cell activation RhoGTPase activating protein (TAGAP) was originally identified through its involvement in human T-cell activation and co-regulation with IL-2 [2]. TAGAP releases GTP from
Total number of patients Female, n (%) Age, mean ± SD (years) Disease duration, mean ± SD (years) Rheumatoid factor positiveness, n (%) Anti-cyclic citrullinated peptide positiveness, n (%)
RA
Controls
135 108 (80) 60.5 ± 12.6 11.7 ± 7.5 98 (73) 99 (73)
147 115 (78) 58.23 ± 5.13
GTP-bound Rho, acts as molecular switch in cells, and modulates cytoskeletal changes [3]. Up today, three TAGAP polymorphisms have been implicated in RA liability of European patients: rs394581, rs212389, and rs182429 [4–7]. Eyre et al. suggested that TAGAP association with RA arises primarily from the polymorphism rs182429 in comparison to the previously reported rs394581 [4,5,7]. However, recently, the rs212389 polymorphism validated as the signal of RA association at the TAGAP locus [6]. Specifically, in this study a comprehensive imputation of CEU HapMap polymorphims in a GWAS was performed [6]. Since no samples were genotyped, we genotyped, for first time, the rs212389 polymorphism in European RA samples. In addition, we extended our genotyping in TAGAP polymorphisms rs394581 and rs182429 as to refine further the causative RA variant. One hundred and thirty-five unrelated RA patients, who satisfied the American College of Rheumatology criteria [8], and 147 healthy volunteers were enrolled in the study. The demographic characteristics of RA patients and controls are shown in Table 1. The polymerase chain reaction-single strand conformation polymorphism analysis coupled with sequencing was used as the screening method for TAGAP variants. The SPSS was used in statistical analysis. All the studied polymorphisms were in Hardy-Weinberg equilibrium in both RA and controls. No significant difference was observed in the distribution of rs394581 and rs182429 between RA patients and controls (P = 0.740, P = 0.361; respectively). However, a trend of statistical significant difference was revealed in rs212389 distribution (P = 0.074). Comparing rs212389 alleles, a straight significant different distribution was also observed (P = 0.018, OR = 0.646, 95% CI: 0.449–0.930) (Table 2). The power of the two sample size groups was estimated to be 76.4% giving that the 74.4% of RA patients carried the rs212389 T allele vs. the 65.3% of control subjects. This is the first study, in which RA samples were genotyped for rs212389 after its identification in a GWAS as a RA
Table 2 Genotypes’ and alleles’ distribution of TAGAP studied polymorphisms in rheumatoid arthritis (RA) patients and controls. TAGAP rs394581 Genotypes
TT
RA n = 135 (%) 75 (55.6) Controls n = 147 (%) 75 (51) P-value Alleles
rs182429 TC
CC
CC
CT
TT
TT
TC
CC
52 (38.5) 63 (42.9) 0.740
8 (5.9) 9 (6.1)
71 (52.6) 65 (44.2)
48 (35.6) 60 (40.8) 0.361
16 (11.9) 22 (15)
76 (56.3) 66 (44.9)
49 (36.3) 60 (40.8) 0.074
10 (7.4) 21 (14.3)
C
C
T
T
T
RA n = 270 (%) 202 (74.8) Controls n = 294 (%) 213 (72.5) P-value OR (95% CI)
rs212389
68 (25.2) 190 (70.4) 81 (27.6) 190 (64.6) 0.524 0.885 (0.608–1.289)
80 (29.6) 104 (35.4) 0.146 0.769 (0.540–1.096)
201 (74.4) 192 (65.3)
C 69 (25.6) 102 (34.7) 0.018 0.646 (0.449–0.930)
544
Letters to the editor / Joint Bone Spine 38 (2013) 541–555
susceptible locus in European subjects [6]. We did not show statistical significant difference in the distribution of polymorphism rs394581 and rs182429 between RA patients and controls as previously reported [6,7]. Consequently, we suggest that polymorphism rs212389 better predicts the association of TAGAP locus with RA. Given that TAGAP is involved in T-cell activation, polymorphisms in TAGAP gene may be very important in autoimmune diseases’ pathogenesis. TAGAP locus has been associated to many autoimmune diseases with opposite effects in many disorders. Therefore, more genetic association studies are needed in larger groups of patients and of different ethnicities in order to fine map the risk polymorphisms in each inflammatory disease, while functional studies of TAGAP protein could help to extend our limited knowledge over its role in cells. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Dieudé P. Rheumatic diseases: environment and genetics. Joint Bone Spine 2009;76:602–7. [2] Mao M, Biery MC, Kobayashi SV, et al. T lymphocyte activation gene identification by coregulated expression on DNA microarrays. Genomics 2004;83: 989–99. [3] Chang IF, Hsiao HY. Induction of RhoGAP and pathological changes characteristic of Alzheimer’s disease by UAHFEMF discharge in rat brain. Curr Alzheimer Res 2005;2:559–69. [4] Stahl EA, Raychaudhuri S, Remmers EF, et al. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet 2010;42:508–14. [5] Raychaudhuri S, Thomson BP, Remmers EF, et al. Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk. Nat Genet 2009;41:1313–8. [6] Chen R, Stahl EA, Kurreeman FA, et al. Fine mapping the TAGAP risk locus in rheumatoid arthritis. Genes Immun 2011;12:314–8. [7] Eyre S, Hinks A, Bowes J, et al. Overlapping genetic susceptibility variants between three autoimmune disorders: rheumatoid arthritis, type 1 diabetes and coeliac disease. Arthritis Res Ther 2010;12:R175. [8] Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315–24.
Osteolytic change of distal interphalangeal joints and sacroiliac joints in subluxing arthropathy associated with anti-Jo-1 antibody
a r t i c l e
i n f o
Keywords: Osteolytic change Arthropathy Anti-Jo-1 antibody Sacroiliac joint
Inflammatory joint symptoms are often seen in idiopathic inflammatory myopathies, including polymyositis (PM). Destructive articular changes are uncommon in PM, but patients with anti-Jo-1 antibody occasionally develop a deforming arthritis. It was first described by Bunch et al. [1] and Oddis et al. [2], and its characteristics are quite different from those of rheumatoid arthritis (RA) in terms of subluxation of the distal interphalangeal (DIP) joints, especially of the thumb IP joints. We describe a case of severe osteolytic changes in DIP joints and sacroiliac joints (SIJ) in subluxing arthropathy with anti-Jo-1 antibody. A 66-year-old woman was admitted to our hospital due to polyarthralgia and muscle pain. She had pain in her fingers for 20 years, considered as having RA in another hospital. Her physical examination revealed symmetric arthritis of the DIP, proximal IP, metacarpophalangeal, wrist, and metatarsopharangeal joints,
Anthoula Chatzikyriakidou a,b Paraskevi V. Voulgari c Alexandros Lambropoulos b Ioannis Georgiou a Alexandros A. Drosos c,∗,1 a Genetics Unit, Department of Obstetrics and Gynaecology, Medical School, University of Ioannina, Ioannina, Greece b Laboratory of General Biology and Genetics, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece c Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110 Ioannina, Greece ∗ Corresponding
author. Tel.: +30 26 51 00 75 03; fax: +30 26 51 00 70 54. E-mail address: [email protected] (A.A. Drosos) 1
www.rheumatology.gr.
Accepted 16 January 2013 Available online 1 March 2013 doi:10.1016/j.jbspin.2013.01.008
Fig. 1. A. Plain radiograph of hands. Osteolytic changes and subluxation of several distal interphalangeal joints in addition to the subluxation of interphalangeal joints and carpometacarpal joints of the thumbs were to be seen. B. Computed tomography scan of sacroiliac joints. Osteolytic change on the iliac side with widening of the joint space was seen without no typical features of spondyloarthropathy including sclerosis, joint space narrowing or ankylosis.
543
Table 1 Rheumatoid arthritis (RA) and control subjects’ characteristics.
References [1] Shadgan B, Menon M, O’Brien PJ, et al. Diagnostic techniques in acute compartment syndrome of the leg. J Orthop Trauma 2008;22:581–7. [2] Mahmud W, Lightfoot JD, Shekhar A. Rhabdomyolysis and compartment syndrome with coadministration of risperidone and simvastatin. J Psychopharmacol 2004;18:432–4. [3] Schneider JM, Roger DJ, Uhl RL. Bilateral forearm compartment syndromes resulting from neuroleptic malignant syndrome. J Hand Surg [Am] 1996;21:287–9. [4] Murdock M, Murdoch MM. Compartment syndrome: a review of the literature. Clin Pediatr Med Surg 2012;29:301–10. [5] Masquelet AC. Traitement chirurgical du syndrome des loges et du syndrome de Volkmann. EMC-Techniques chirurgicales-Orthopédie-Traumatologie 2001:44–078.
Goulven Rochcongar a,∗ Gwenola Maigné b Vincent Pineau a Christophe Hulet a a Department of Orthopaedic and Traumatology, CHU de Caen, avenue Côte-de-Nacre, 14003 Caen cedex 9, France b Department of Internal Medicine, CHU de Caen, avenue Côte-de-Nacre, 14003 Caen cedex 9, France ∗ Corresponding
author. Tel.: +33 06 48 13 24 16; fax: +33 02 31 06 48 90. E-mail addresses: [email protected], [email protected] (G. Rochcongar) Accepted 11 January 2013 Available online 6 April 2013
doi:10.1016/j.jbspin.2013.02.006
Validation of the TAGAP rs212389 polymorphism in rheumatoid arthritis susceptibility
a r t i c l e
i n f o
Keywords: Rheumatoid arthritis Polymorphism TAGAP
Rheumatoid arthritis (RA) is a chronic inflammatory disorder in which both genetic and environmental factors have been implicated [1]. T-cell activation RhoGTPase activating protein (TAGAP) was originally identified through its involvement in human T-cell activation and co-regulation with IL-2 [2]. TAGAP releases GTP from
Total number of patients Female, n (%) Age, mean ± SD (years) Disease duration, mean ± SD (years) Rheumatoid factor positiveness, n (%) Anti-cyclic citrullinated peptide positiveness, n (%)
RA
Controls
135 108 (80) 60.5 ± 12.6 11.7 ± 7.5 98 (73) 99 (73)
147 115 (78) 58.23 ± 5.13
GTP-bound Rho, acts as molecular switch in cells, and modulates cytoskeletal changes [3]. Up today, three TAGAP polymorphisms have been implicated in RA liability of European patients: rs394581, rs212389, and rs182429 [4–7]. Eyre et al. suggested that TAGAP association with RA arises primarily from the polymorphism rs182429 in comparison to the previously reported rs394581 [4,5,7]. However, recently, the rs212389 polymorphism validated as the signal of RA association at the TAGAP locus [6]. Specifically, in this study a comprehensive imputation of CEU HapMap polymorphims in a GWAS was performed [6]. Since no samples were genotyped, we genotyped, for first time, the rs212389 polymorphism in European RA samples. In addition, we extended our genotyping in TAGAP polymorphisms rs394581 and rs182429 as to refine further the causative RA variant. One hundred and thirty-five unrelated RA patients, who satisfied the American College of Rheumatology criteria [8], and 147 healthy volunteers were enrolled in the study. The demographic characteristics of RA patients and controls are shown in Table 1. The polymerase chain reaction-single strand conformation polymorphism analysis coupled with sequencing was used as the screening method for TAGAP variants. The SPSS was used in statistical analysis. All the studied polymorphisms were in Hardy-Weinberg equilibrium in both RA and controls. No significant difference was observed in the distribution of rs394581 and rs182429 between RA patients and controls (P = 0.740, P = 0.361; respectively). However, a trend of statistical significant difference was revealed in rs212389 distribution (P = 0.074). Comparing rs212389 alleles, a straight significant different distribution was also observed (P = 0.018, OR = 0.646, 95% CI: 0.449–0.930) (Table 2). The power of the two sample size groups was estimated to be 76.4% giving that the 74.4% of RA patients carried the rs212389 T allele vs. the 65.3% of control subjects. This is the first study, in which RA samples were genotyped for rs212389 after its identification in a GWAS as a RA
Table 2 Genotypes’ and alleles’ distribution of TAGAP studied polymorphisms in rheumatoid arthritis (RA) patients and controls. TAGAP rs394581 Genotypes
TT
RA n = 135 (%) 75 (55.6) Controls n = 147 (%) 75 (51) P-value Alleles
rs182429 TC
CC
CC
CT
TT
TT
TC
CC
52 (38.5) 63 (42.9) 0.740
8 (5.9) 9 (6.1)
71 (52.6) 65 (44.2)
48 (35.6) 60 (40.8) 0.361
16 (11.9) 22 (15)
76 (56.3) 66 (44.9)
49 (36.3) 60 (40.8) 0.074
10 (7.4) 21 (14.3)
C
C
T
T
T
RA n = 270 (%) 202 (74.8) Controls n = 294 (%) 213 (72.5) P-value OR (95% CI)
rs212389
68 (25.2) 190 (70.4) 81 (27.6) 190 (64.6) 0.524 0.885 (0.608–1.289)
80 (29.6) 104 (35.4) 0.146 0.769 (0.540–1.096)
201 (74.4) 192 (65.3)
C 69 (25.6) 102 (34.7) 0.018 0.646 (0.449–0.930)
544
Letters to the editor / Joint Bone Spine 38 (2013) 541–555
susceptible locus in European subjects [6]. We did not show statistical significant difference in the distribution of polymorphism rs394581 and rs182429 between RA patients and controls as previously reported [6,7]. Consequently, we suggest that polymorphism rs212389 better predicts the association of TAGAP locus with RA. Given that TAGAP is involved in T-cell activation, polymorphisms in TAGAP gene may be very important in autoimmune diseases’ pathogenesis. TAGAP locus has been associated to many autoimmune diseases with opposite effects in many disorders. Therefore, more genetic association studies are needed in larger groups of patients and of different ethnicities in order to fine map the risk polymorphisms in each inflammatory disease, while functional studies of TAGAP protein could help to extend our limited knowledge over its role in cells. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Dieudé P. Rheumatic diseases: environment and genetics. Joint Bone Spine 2009;76:602–7. [2] Mao M, Biery MC, Kobayashi SV, et al. T lymphocyte activation gene identification by coregulated expression on DNA microarrays. Genomics 2004;83: 989–99. [3] Chang IF, Hsiao HY. Induction of RhoGAP and pathological changes characteristic of Alzheimer’s disease by UAHFEMF discharge in rat brain. Curr Alzheimer Res 2005;2:559–69. [4] Stahl EA, Raychaudhuri S, Remmers EF, et al. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet 2010;42:508–14. [5] Raychaudhuri S, Thomson BP, Remmers EF, et al. Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk. Nat Genet 2009;41:1313–8. [6] Chen R, Stahl EA, Kurreeman FA, et al. Fine mapping the TAGAP risk locus in rheumatoid arthritis. Genes Immun 2011;12:314–8. [7] Eyre S, Hinks A, Bowes J, et al. Overlapping genetic susceptibility variants between three autoimmune disorders: rheumatoid arthritis, type 1 diabetes and coeliac disease. Arthritis Res Ther 2010;12:R175. [8] Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315–24.
Osteolytic change of distal interphalangeal joints and sacroiliac joints in subluxing arthropathy associated with anti-Jo-1 antibody
a r t i c l e
i n f o
Keywords: Osteolytic change Arthropathy Anti-Jo-1 antibody Sacroiliac joint
Inflammatory joint symptoms are often seen in idiopathic inflammatory myopathies, including polymyositis (PM). Destructive articular changes are uncommon in PM, but patients with anti-Jo-1 antibody occasionally develop a deforming arthritis. It was first described by Bunch et al. [1] and Oddis et al. [2], and its characteristics are quite different from those of rheumatoid arthritis (RA) in terms of subluxation of the distal interphalangeal (DIP) joints, especially of the thumb IP joints. We describe a case of severe osteolytic changes in DIP joints and sacroiliac joints (SIJ) in subluxing arthropathy with anti-Jo-1 antibody. A 66-year-old woman was admitted to our hospital due to polyarthralgia and muscle pain. She had pain in her fingers for 20 years, considered as having RA in another hospital. Her physical examination revealed symmetric arthritis of the DIP, proximal IP, metacarpophalangeal, wrist, and metatarsopharangeal joints,
Anthoula Chatzikyriakidou a,b Paraskevi V. Voulgari c Alexandros Lambropoulos b Ioannis Georgiou a Alexandros A. Drosos c,∗,1 a Genetics Unit, Department of Obstetrics and Gynaecology, Medical School, University of Ioannina, Ioannina, Greece b Laboratory of General Biology and Genetics, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece c Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110 Ioannina, Greece ∗ Corresponding
author. Tel.: +30 26 51 00 75 03; fax: +30 26 51 00 70 54. E-mail address: [email protected] (A.A. Drosos) 1
www.rheumatology.gr.
Accepted 16 January 2013 Available online 1 March 2013 doi:10.1016/j.jbspin.2013.01.008
Fig. 1. A. Plain radiograph of hands. Osteolytic changes and subluxation of several distal interphalangeal joints in addition to the subluxation of interphalangeal joints and carpometacarpal joints of the thumbs were to be seen. B. Computed tomography scan of sacroiliac joints. Osteolytic change on the iliac side with widening of the joint space was seen without no typical features of spondyloarthropathy including sclerosis, joint space narrowing or ankylosis.