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P56 Single nucleotide polymorphisms (SNP) in genes coding for methotrexate (MTX) metabolism in Indian rheumatoid arthritis (RA) patients
S43
Indian Journal of Rheumatology 2008 November; Vol. 3, No. 3 (Suppl)
Poster presentations
P56 Single nucleotide polymorphisms (SNP) in genes coding for methotrexate (MTX) metabolism in Indian rheumatoid arthritis (RA) patients
P58 Role of ceruloplasmin as prognostic marker in rheumatoid arthritis by a novel method of ceruloplasmin estimation
Y Ghodke1, A Chopra3, P Shintre4, K Joshi4 and B Patwardhan2
N Kumar, LT Col, K Shanmuganandan, BL Somani, V Ambade
Department of Health Science, 2Interdisciplinary School of Health Sciences, University of Pune, 3Centre for Rheumatic Diseases, 4Department of Biotechnology, Sinhgad College of Engineering, Pune, India.
Department of Rheumatology, Command Hospital (Southern Command), Armed Forces Medical College, Pune, India. Introduction: Rheumatoid arthritis is a chronic, inflammatory, multisystem autoimmune disorder. Ceruloplasmin is one of the important acute phase reactants implicated in rheumatoid arthritis. Ceruloplasmin level is raised in rheumatoid arthritis and the serum ceruloplasmin levels can be measured to see if there is any progressive and proportionate decrease in it as the medication advances. Methodology: Thirty diagnosed patients of rheumatoid arthritis were included. The number of tender and swollen joints was counted. Relevant investigations including erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP) was done. Disease activity scoring was done by DAS28 = 0.56* √ (tender28) + 0.28* √ (swollen28) + 0.70* ln (ESR) + 0.014* GH serum ceruloplasmin level measured by the patented method of Somani BL and Ambade V was correlated with DAS score using appropriate statistical analysis. Serum ceruloplasmin levels and DAS28 was measured after 3 months. Results were collected and statistical analysis was done. Results and conclusion: Serum ceruloplasmin levels were increased in patients with active rheumatoid arthritis as determined by DAS28. Serum ceruloplasmin decreased with 3 months of treatment with DMARDs. This decrease was statistically significant and correlated with decrease in disease activity by DAS28.
1
MTX is among the best tolerated DMARD but is limited by major interpatient variability in clinical response and unpredictable toxicity. Though gene polymorphism of the intracellular MTX metabolic pathway is published recently little is known about Indian population. We report data from Indian patients of RA evaluated and treated in CRD, Pune. Methods: Naive RA patients (n = 336) completing at least 1 year of supervised MTX were selected (according to clinic attendance) from a busy community rheumatology referral clinic from May 2007 to January 2008. We retrospectively analyzed data extracted from CRD database; but recalled patients to confirm events. 144 unrelated healthy controls (HC) were chosen. Post consent, peripheral blood genomic DNA (Miller’s protocol) was extracted. PCRRFLP (oligonucleotides-Integrated Biotechnologies, restriction endonucleases-New England Biolabs) and Real-time Taqman allelic discrimination (Applied Biosystems) for genotyping was performed. 12 polymorphisms in 9 genes of MTX metabolism (including transporters) were studied; MTHFR: methylenetetrahydrofoate reductase; TS: thymidylate synthase; RFC1: reduce folate carrier 1; MS: methionine synthase; SHMT1: Serine hydroxymethyltransferase 1; MDR1: multidrug resistant protein 1; GGH: γ glutamyl hydrolase; ATIC: aminoimidazol carboxamide ribonucleotide transformylase; MTRR: methionine synthase reductase. Results: We present odd’s ratio (OR) of significant associations (95% confidence interval/CI) (Table 1). Polymorphism
P59 Randomized clinical trial of dose variable (10-mg vs 40-mg) study of local methylprednisolone acetate injection in carpal tunnel syndrome
RA (n = 336)
HC (n = 144)
P value
Odd’s Ratio (95% CI)
MTHFR A1298C AA CC
0.29 0.31
0.48 0.05
P < 0.0001 P < 0.0001
0.4 (0.3–0.6) 7.6 (3.6–16.1)
TS 3 UTR 6bp/6bp
1 Department of Medicine and 3Surgery, Government Medical College and Hospital, Chandigarh, 2Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
0.20
0.31
0.6 (0.4–0.9)
RFC1G80A GG GA AA
0.37 0.47 0.16
0.27 0.33 0.40
Introduction: The treatment of idiopathic carpel tunnel syndrome is not well defined especially in patients with mild to moderate severity. Local corticosteroid injection therapy in has been reported to have short lasting effect and high recurrence rate. Moreover the dose is also not well defined in this prospective randomized study, we evaluated the long term efficacy of 10 mg vs 40 mg dose of local methylprednisolone acetate injection in patients with CTS.
MSA2756G AG
0.36
0.51
0.003
0.6 (0.4–0.8)
SHMT1 C1420T CT
0.26
0.36
0.046
0.6 (0.4–1)
S Chauhan1, V Agarwal2, R Singh1, Wiclaf1, R Singh3, S D’Cruz1, A Sachdev1
0.011 0.027 0.004 P < 0.0001
1.6 (1.05–2.5) 1.8 (1.2–2.7) 0.3 (0.2–0.4)
Conclusion: Significant associations in genes coding MTX is observed in our cohort of RA. These associations can be further explored to examine MTX response (efficacy and toxicity). Acknowledgement: (1) CSIR (for rewarding Senior Research Fellowship to YG) (2) CRD for providing logistic and patient support (Ms Anuradha V and Ms Manjit S) (3) National Center for Cell Sciences, Pune (Dr Anand Hardikar, Mr Amrutesh Puranik).
P57 Rheumatoid arthritis: phenomenology, personality profile, stress and their inter-relationship LA Gauri, LN Gupta, H Yadav, S Prasad Department of Medicine, S.P. Medical College, Bikaner, India. Background: This prospective study was conducted to study the psychiatric morbidity of rheumatoid arthritis and to look for an association between disease parameters and personality dimensions of rheumatoid arthritis patients. Methods: Forty patients were selected from Rheumatology clinic of PBM Hospital, Bikaner diagnosed as per American College of Rheumatology (ACR) revised criteria. The ICD-10 module of International Personality Disorder Examination (IPDE), social and occupational functioning assessment scale (SOFAS), Hamilton’s rating scale for depression (HAM–D), presumptive stressful life events scale (PSLE) were administered to these patients. Bivariate statistical methods were used to find association between illness variables and psychological dimensions. Group differences were analysed by students t-test and ANOVA. Results: Rheumatoid arthritis patients with psychiatric morbidity showed higher rheumatoid arthritis severity (P < 0.02), swan neck and valgus deformity (P < 0.05), more number of joints involved (P < 0.01), smaller joints (metacarpo-phalngeal and interphalangeal) involvement (P < 0.05), presence of c-reative protein in blood samples (P < 0.01). Majority of patients who had personality psychopathology also reported stress in preceding 1 year period. Conclusion: Personality level psychopathology—either alone or in combination is present in 17 patients i.e. 42.5% of whole sample. Patients with single personality trait psychopathology were better in comparison with severe level personality psychopathology in terms of number of joints involved, joint deformities, social and occupational functioning and psychiatric morbidity.
Patients and methods: Patients of idiopathic CTS were recruited from the outpatient clinic of department of medicine and were randomized to receive either 10-mg or 40-mg dose of methylprednisolone acetate injection into the carpal canal. Clinical (using boston severity scale) and electrophysiological evaluation was carried out at baseline. Each patient was evaluated at 3 monthly intervals for one year. Those who had relapse within a year were given a second dose injection with the same dose as the first and those who had a second relapse were subjected to surgery. Results: There were 58 patients, 28 (41 hands) randomized to 10-mg group and 30 (45 hands) to 40-mg group. At baseline the mean age, sex distribution, duration of disease, symptom severity score and functional scores were comparable between the two groups. At 3 months, distal motor latencies (DML), symptom severity score and functional scores improved in 10-mg group (P = 0.006, P = 0.0005 and P = 0.07 respectively) and 40-mg group (P = 0.03, P = 0.0001 and P = 0.03 respectively). At 12 months, DML, symptom severity scores and functional scores continued to show significant improvement for the two groups. The comparative total percentage improvement between the two groups for the above parameters at both 3 and 12 months was not significant. Only 4 hands required surgery (one in 10 mg group and three in 40 mg group). Conclusion: We conclude that there is long term efficacy of local corticosteroid injections and 10-mg methyl prednisolone acetate is as effective as 40-mg in relieving the symptoms and improving the electrophysiological parameters.
P60 Family with type 1 Stickler syndrome S Vinay Department of Rheumatology, Command Hospital (WC) Chandimandir. We report a case of 54 years old individual with chronic backache and polyarthralgias. He was suspected to be a case of Ankylosing spondylitis as he had Kyphosis and stooped posture. Evaluation revealed there was no evidence of sacroilitis on CT scan of SI joints. Patient had osteoarthritis both knees. He also had Characteristic face with flat nasal bridge, and Micrognathia, Echocardiography revealed mitral valve prolapse. Also he had sensorineural deafness, and myopia. Family history revealed he has daughter 24 years old and son 27 years old. Both siblings have severe sensorineural deafness myopia and facies similar to their father. However they do not have skeletal symptoms. Clinical diagnosis of Stickler syndrome is suspected based on diagnostic criteria for Type 1 Stickler syndrome by Rose et al. (2005) Stickler syndrome is among the most common autosomal dominant connective tissue disorders but is often unrecognized. Early, identification of ocular and auditory abnormalities allows surveillance for and early treatment of complications. Similarly, correct diagnosis allows surveillance for skeletal complications and genetic counseling for affected patients and families.
Indian Journal of Rheumatology 2008 November; Vol. 3, No. 3 (Suppl)
Poster presentations
P56 Single nucleotide polymorphisms (SNP) in genes coding for methotrexate (MTX) metabolism in Indian rheumatoid arthritis (RA) patients
P58 Role of ceruloplasmin as prognostic marker in rheumatoid arthritis by a novel method of ceruloplasmin estimation
Y Ghodke1, A Chopra3, P Shintre4, K Joshi4 and B Patwardhan2
N Kumar, LT Col, K Shanmuganandan, BL Somani, V Ambade
Department of Health Science, 2Interdisciplinary School of Health Sciences, University of Pune, 3Centre for Rheumatic Diseases, 4Department of Biotechnology, Sinhgad College of Engineering, Pune, India.
Department of Rheumatology, Command Hospital (Southern Command), Armed Forces Medical College, Pune, India. Introduction: Rheumatoid arthritis is a chronic, inflammatory, multisystem autoimmune disorder. Ceruloplasmin is one of the important acute phase reactants implicated in rheumatoid arthritis. Ceruloplasmin level is raised in rheumatoid arthritis and the serum ceruloplasmin levels can be measured to see if there is any progressive and proportionate decrease in it as the medication advances. Methodology: Thirty diagnosed patients of rheumatoid arthritis were included. The number of tender and swollen joints was counted. Relevant investigations including erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP) was done. Disease activity scoring was done by DAS28 = 0.56* √ (tender28) + 0.28* √ (swollen28) + 0.70* ln (ESR) + 0.014* GH serum ceruloplasmin level measured by the patented method of Somani BL and Ambade V was correlated with DAS score using appropriate statistical analysis. Serum ceruloplasmin levels and DAS28 was measured after 3 months. Results were collected and statistical analysis was done. Results and conclusion: Serum ceruloplasmin levels were increased in patients with active rheumatoid arthritis as determined by DAS28. Serum ceruloplasmin decreased with 3 months of treatment with DMARDs. This decrease was statistically significant and correlated with decrease in disease activity by DAS28.
1
MTX is among the best tolerated DMARD but is limited by major interpatient variability in clinical response and unpredictable toxicity. Though gene polymorphism of the intracellular MTX metabolic pathway is published recently little is known about Indian population. We report data from Indian patients of RA evaluated and treated in CRD, Pune. Methods: Naive RA patients (n = 336) completing at least 1 year of supervised MTX were selected (according to clinic attendance) from a busy community rheumatology referral clinic from May 2007 to January 2008. We retrospectively analyzed data extracted from CRD database; but recalled patients to confirm events. 144 unrelated healthy controls (HC) were chosen. Post consent, peripheral blood genomic DNA (Miller’s protocol) was extracted. PCRRFLP (oligonucleotides-Integrated Biotechnologies, restriction endonucleases-New England Biolabs) and Real-time Taqman allelic discrimination (Applied Biosystems) for genotyping was performed. 12 polymorphisms in 9 genes of MTX metabolism (including transporters) were studied; MTHFR: methylenetetrahydrofoate reductase; TS: thymidylate synthase; RFC1: reduce folate carrier 1; MS: methionine synthase; SHMT1: Serine hydroxymethyltransferase 1; MDR1: multidrug resistant protein 1; GGH: γ glutamyl hydrolase; ATIC: aminoimidazol carboxamide ribonucleotide transformylase; MTRR: methionine synthase reductase. Results: We present odd’s ratio (OR) of significant associations (95% confidence interval/CI) (Table 1). Polymorphism
P59 Randomized clinical trial of dose variable (10-mg vs 40-mg) study of local methylprednisolone acetate injection in carpal tunnel syndrome
RA (n = 336)
HC (n = 144)
P value
Odd’s Ratio (95% CI)
MTHFR A1298C AA CC
0.29 0.31
0.48 0.05
P < 0.0001 P < 0.0001
0.4 (0.3–0.6) 7.6 (3.6–16.1)
TS 3 UTR 6bp/6bp
1 Department of Medicine and 3Surgery, Government Medical College and Hospital, Chandigarh, 2Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
0.20
0.31
0.6 (0.4–0.9)
RFC1G80A GG GA AA
0.37 0.47 0.16
0.27 0.33 0.40
Introduction: The treatment of idiopathic carpel tunnel syndrome is not well defined especially in patients with mild to moderate severity. Local corticosteroid injection therapy in has been reported to have short lasting effect and high recurrence rate. Moreover the dose is also not well defined in this prospective randomized study, we evaluated the long term efficacy of 10 mg vs 40 mg dose of local methylprednisolone acetate injection in patients with CTS.
MSA2756G AG
0.36
0.51
0.003
0.6 (0.4–0.8)
SHMT1 C1420T CT
0.26
0.36
0.046
0.6 (0.4–1)
S Chauhan1, V Agarwal2, R Singh1, Wiclaf1, R Singh3, S D’Cruz1, A Sachdev1
0.011 0.027 0.004 P < 0.0001
1.6 (1.05–2.5) 1.8 (1.2–2.7) 0.3 (0.2–0.4)
Conclusion: Significant associations in genes coding MTX is observed in our cohort of RA. These associations can be further explored to examine MTX response (efficacy and toxicity). Acknowledgement: (1) CSIR (for rewarding Senior Research Fellowship to YG) (2) CRD for providing logistic and patient support (Ms Anuradha V and Ms Manjit S) (3) National Center for Cell Sciences, Pune (Dr Anand Hardikar, Mr Amrutesh Puranik).
P57 Rheumatoid arthritis: phenomenology, personality profile, stress and their inter-relationship LA Gauri, LN Gupta, H Yadav, S Prasad Department of Medicine, S.P. Medical College, Bikaner, India. Background: This prospective study was conducted to study the psychiatric morbidity of rheumatoid arthritis and to look for an association between disease parameters and personality dimensions of rheumatoid arthritis patients. Methods: Forty patients were selected from Rheumatology clinic of PBM Hospital, Bikaner diagnosed as per American College of Rheumatology (ACR) revised criteria. The ICD-10 module of International Personality Disorder Examination (IPDE), social and occupational functioning assessment scale (SOFAS), Hamilton’s rating scale for depression (HAM–D), presumptive stressful life events scale (PSLE) were administered to these patients. Bivariate statistical methods were used to find association between illness variables and psychological dimensions. Group differences were analysed by students t-test and ANOVA. Results: Rheumatoid arthritis patients with psychiatric morbidity showed higher rheumatoid arthritis severity (P < 0.02), swan neck and valgus deformity (P < 0.05), more number of joints involved (P < 0.01), smaller joints (metacarpo-phalngeal and interphalangeal) involvement (P < 0.05), presence of c-reative protein in blood samples (P < 0.01). Majority of patients who had personality psychopathology also reported stress in preceding 1 year period. Conclusion: Personality level psychopathology—either alone or in combination is present in 17 patients i.e. 42.5% of whole sample. Patients with single personality trait psychopathology were better in comparison with severe level personality psychopathology in terms of number of joints involved, joint deformities, social and occupational functioning and psychiatric morbidity.
Patients and methods: Patients of idiopathic CTS were recruited from the outpatient clinic of department of medicine and were randomized to receive either 10-mg or 40-mg dose of methylprednisolone acetate injection into the carpal canal. Clinical (using boston severity scale) and electrophysiological evaluation was carried out at baseline. Each patient was evaluated at 3 monthly intervals for one year. Those who had relapse within a year were given a second dose injection with the same dose as the first and those who had a second relapse were subjected to surgery. Results: There were 58 patients, 28 (41 hands) randomized to 10-mg group and 30 (45 hands) to 40-mg group. At baseline the mean age, sex distribution, duration of disease, symptom severity score and functional scores were comparable between the two groups. At 3 months, distal motor latencies (DML), symptom severity score and functional scores improved in 10-mg group (P = 0.006, P = 0.0005 and P = 0.07 respectively) and 40-mg group (P = 0.03, P = 0.0001 and P = 0.03 respectively). At 12 months, DML, symptom severity scores and functional scores continued to show significant improvement for the two groups. The comparative total percentage improvement between the two groups for the above parameters at both 3 and 12 months was not significant. Only 4 hands required surgery (one in 10 mg group and three in 40 mg group). Conclusion: We conclude that there is long term efficacy of local corticosteroid injections and 10-mg methyl prednisolone acetate is as effective as 40-mg in relieving the symptoms and improving the electrophysiological parameters.
P60 Family with type 1 Stickler syndrome S Vinay Department of Rheumatology, Command Hospital (WC) Chandimandir. We report a case of 54 years old individual with chronic backache and polyarthralgias. He was suspected to be a case of Ankylosing spondylitis as he had Kyphosis and stooped posture. Evaluation revealed there was no evidence of sacroilitis on CT scan of SI joints. Patient had osteoarthritis both knees. He also had Characteristic face with flat nasal bridge, and Micrognathia, Echocardiography revealed mitral valve prolapse. Also he had sensorineural deafness, and myopia. Family history revealed he has daughter 24 years old and son 27 years old. Both siblings have severe sensorineural deafness myopia and facies similar to their father. However they do not have skeletal symptoms. Clinical diagnosis of Stickler syndrome is suspected based on diagnostic criteria for Type 1 Stickler syndrome by Rose et al. (2005) Stickler syndrome is among the most common autosomal dominant connective tissue disorders but is often unrecognized. Early, identification of ocular and auditory abnormalities allows surveillance for and early treatment of complications. Similarly, correct diagnosis allows surveillance for skeletal complications and genetic counseling for affected patients and families.