Angelo Gaffo

Publications (28) View all

• Article: Impact of interactions of cigarette smoking with NAT2 polymorphisms on rheumatoid arthritis risk in African Americans.

  Ted R Mikuls, Tricia Levan, Karen A Gould, Fang Yu, Geoffrey M Thiele, Kimberly K Bynote, Doyt Conn, Beth L Jonas, Leigh F Callahan, Edwin Smith, Richard Brasington, Larry W Moreland, Richard Reynolds, Angelo Gaffo, S Louis Bridges
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  ABSTRACT: To examine whether polymorphisms in genes coding for drug-metabolizing enzymes (DMEs) have an impact on rheumatoid arthritis (RA) risk due to cigarette smoking in African Americans. Smoking status was evaluated in African American patients with RA compared with non-RA controls, with smoking exposure categorized as heavy smoker (≥10 pack-years) versus never smoker/<10 pack-years. Individuals were genotyped for a homozygous deletion polymorphism in the M1 gene loci of glutathione S-transferase (GSTM1-null) in addition to tagging single-nucleotide polymorphisms (SNPs) in N-acetyltransferase 1 (NAT1), NAT2, and epoxide hydrolase 1 (EPXH1). Associations of these genotypes with RA risk were examined using logistic regression, and gene-smoking interactions were assessed. There were no significant associations of any DME genotype with RA. After adjustment for multiple comparisons, there were significant additive interactions between heavy smoking and the NAT2 SNPs rs9987109 (P(additive) = 0.000003) and rs1208 (P(additive) = 0.00001); the attributable proportion due to interaction ranged from 0.61 to 0.67. None of the multiplicative gene-smoking interactions examined remained significant with regard to overall disease risk, after adjustment for multiple testing. There was no evidence of significant gene-smoking interactions in analyses of GSTM1-null, NAT1, or EPXH1. DME gene-smoking interactions were similar when cases were limited to those patients who were positive for anti-citrullinated protein antibodies. Among African Americans, RA risk imposed by heavy smoking appears to be mediated in part by genetic variation in NAT2. While further studies are needed to elucidate the mechanisms underpinning these interactions, these SNPs appear to identify African American smokers at a much higher risk for RA, in whom the relative risk is at least 2-fold higher when compared to nonsmokers lacking these risk alleles.
  Arthritis & Rheumatism 03/2012; 64(3):655-64. · 7.87 Impact Factor
• Source

  Available from: PubMed Central

  Article: Association between being African-American, serum urate levels and the risk of developing hyperuricemia: findings from the Coronary Artery Risk Development in Young Adults cohort.

  Angelo L Gaffo, David R Jacobs, Cora E Lewis, Ted R Mikuls, Kenneth G Saag
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  ABSTRACT: Findings that African-American race/ethnicity is associated with higher concentrations of serum urate have not been adjusted for possible confounding factors or have not explored this question as a primary outcome. We tested this hypothesis in a bi-racial cohort of younger African-American and white men and women. Data from 5,049 participants at the Coronary Artery Risk Development in Young Adults (CARDIA) cohort baseline (1985 to 1986) and follow-up for up to 20 years of individuals without hyperuricemia (defined as a serum urate of 6.8 mg/dL or more) at baseline were utilized. We determined associations between race, serum urate and the development of hyperuricemia in sex-specific cross-sectional and longitudinal analyses. Confounding factors examined included: age at enrollment, body mass index, development of hypertension, glomerular filtration rate, medication use, diet and alcohol intake and menopausal symptoms in women. Referent to whites, African-American men and women had significantly lower concentrations of serum urate at baseline. African-American men had an essentially equal risk of developing incident hyperuricemia during follow-up compared with white men (multivariable adjusted HR = 1.12 (0.88 to 1.40)). African-American women developed a significantly increased risk of hyperuricemia when compared to white women (HR = 2.31 (1.34 to 3.99)). Young African-American men and women had lower concentrations of serum urate than whites. During longitudinal follow-up, African-American women had a significantly increased risk of developing hyperuricemia when compared with white women, a difference that was not observed in men. Differences in production of serum urate or a more rapid decline in fractional excretion of serum urate are potential, albeit still unproven, explanations for these findings in African-American women.
  Arthritis research & therapy 01/2012; 14(1):R4. · 4.27 Impact Factor
• Article: Drug treatment of hyperuricemia to prevent cardiovascular outcomes: are we there yet?

  Angelo L Gaffo, Kenneth G Saag
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  ABSTRACT: Data supporting an association between high levels of serum urate and cardiovascular disease have continued to emerge. Basic science data, small clinical trials, and epidemiologic studies have provided support for the idea of a true causal effect. In this paper, we present evidence about the association between hyperuricemia and selected cardiovascular diseases. Although data generated so far compellingly support pharmacologic urate-lowering therapy in selected cases with high cardiovascular risk, further evidence is necessary before widely advocating this approach to prevent cardiovascular outcomes putatively associated with hyperuricemia.
  American Journal of Cardiovascular Drugs 12/2011; 12(1):1-6. · 1.77 Impact Factor
• Article: Developing a provisional definition of flare in patients with established gout.

  Angelo L Gaffo, H Ralph Schumacher, Kenneth G Saag, William J Taylor, Janet Dinnella, Ryan Outman, Lang Chen, Nicola Dalbeth, Francisca Sivera, Janitzia Vázquez-Mellado, Chung-Tei Chou, Xuejun Zeng, Fernando Perez-Ruiz, Sergio C Kowalski, Claudia Goldenstein-Schainberg, Lan Chen, Thomas Bardin, Jasvinder A Singh
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  ABSTRACT: Various nonvalidated criteria for disease flare have been used in studies of gout. Our objective was to develop empirical definitions for a gout flare from patient-reported features. Possible elements for flare criteria were previously reported. Data were collected from 210 gout patients at 8 international sites to evaluate potential gout flare criteria against the gold standard of an expert rheumatologist definition. Flare definitions based on the presence of the number of criteria independently associated with the flare and classification and regression tree approaches were developed. The mean ± SD age of the study participants was 56.2 ± 15 years, 207 of them (98%) were men, and 54 of them (26%) had flares of gout. The presence of any patient-reported warm joint, any patient-reported swollen joint, patient-reported pain at rest score of >3 (0-10 scale), and patient-reported flare were independently associated with the study gold standard. The greatest discriminating power was noted for the presence of 3 or more of the above 4 criteria (sensitivity 91% and specificity 82%). Requiring all 4 criteria provided the highest specificity (96%) and positive predictive value (85%). A classification tree identified pain at rest with a score of >3, followed by patient self-reported flare, as the rule associated with the gold standard (sensitivity 83% and specificity 90%). We propose definitions for a disease flare based on self-reported items in patients previously diagnosed as having gout. Patient-reported flare, joint pain at rest, warm joints, and swollen joints were most strongly associated with presence of a gout flare. These provisional definitions will next be validated in clinical trials.
  Arthritis & Rheumatism 11/2011; 64(5):1508-17. · 7.87 Impact Factor
• Article: Patient-reported outcomes in chronic gout: a report from OMERACT 10.

  Jasvinder A Singh, Will J Taylor, Lee S Simon, Puja P Khanna, Lisa K Stamp, Fiona M McQueen, Tuhina Neogi, Angelo L Gaffo, Michael A Becker, Patricia A MacDonald, Omar Dabbous, Vibeke Strand, Nicola D Dalbeth, Daniel Aletaha, N Lawrence Edwards, H Ralph Schumacher
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  ABSTRACT: To summarize the endorsement of measures of patient-reported outcome (PRO) domains in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10). During the OMERACT 10 gout workshop, validation data were presented for key PRO domains including pain [pain by visual analog scale (VAS)], patient global (patient global VAS), activity limitation [Health Assessment Questionnaire-Disability Index (HAQ-DI)], and a disease-specific measure, the Gout Assessment Questionnaire version 2.0 (GAQ v2.0). Data were presented on all 3 aspects of the OMERACT filters of truth, discrimination, and feasibility. One PRO, health-related quality of life measurement with the Medical Outcomes Study Short-form 36 (SF-36), was previously endorsed at OMERACT 9. One measure for each of the 3 PRO of pain, patient global, and activity limitation was endorsed by > 70% of the OMERACT delegates to have appropriate validation data. Specifically, pain measurement by VAS was endorsed by 85%, patient global assessment by VAS by 73%, and activity limitation by HAQ-DI by 71%. GAQ v2.0 received 30% vote and was not endorsed due to several concerns including low internal consistency and lack of familiarity with the measure. More validation studies are needed for this measure. With the endorsement of one measure each for pain, patient global, SF-36, and activity limitation, all 4 PRO for chronic gout have been endorsed. Future validation studies are needed for the disease-specific measure, GAQ v2.0. Validation for PRO for acute gout will be the focus of the next validation exercise for the OMERACT gout group.
  The Journal of Rheumatology 07/2011; 38(7):1452-7. · 3.69 Impact Factor