title: Association study involving polymorphisms in IL-6, IL-1RA, and CTLA4 genes and rheumatic heart disease in New Zealand population of Māori and Pacific ancestry.
abstract: Rheumatic fever (RF) incidence among New Zealand (NZ) individuals of Polynesian (Māori and Pacific) ancestry remains among the highest in the world. Polymorphisms in the IL-6, IL1RN, and CTLA4 genes have been associated with RF, and their products are modulated by new medications. Confirmation of these previous associations could help guide clinical approaches. We aimed to test IL-6, IL-1RA (IL1RN), and CTLA4 functional SNPs in 204 rheumatic heart disease (RHD) patients and 116 controls of Māori and Pacific ancestry.
  
  
  
  Self-reported ancestry of the eight great-grandparents defined ancestry of participants. Severity of carditis was classified according to the 2012 World Heart Federation guideline for the echocardiographic diagnosis of RHD. The IL-6 promoter rs1800797, IL1RN rs447713 and CTLA4 rs3087243 SNPs were genotyped by Taqman. Correlations were assessed by logistic regression analysis adjusting for gender and ancestry.
  
  
  
  The IL-6 rs1800797 variant was significantly associated with RHD with carriers of the GG genotype 6.09 (CI 1.23; 30.23) times more likely to develop RHD than the carriers of the AA genotype (P=0.027). No significant associations with RHD were found for the IL1RN rs447713 and CTLA4 rs3087243 SNPs. Patients carrying the G allele (GG plus AG genotype) for the IL1RN rs447713 SNP had 2.36 times (CI 1.00; 5.56) more severe carditis than those without this allele (the AA genotype) (P=0.049).
  
  
  
  The IL-6 promoter rs1800797 (-597G/A) SNP may influence susceptibility to RHD of people of Māori and Pacific ancestry living in NZ. The IL1RN rs447713 SNP may influence the severity of carditis in this population.
authors.affiliation: Instituto Israelita de Ensino e Pesquisa Albert Einstein, Hospital Israelita Albert Einstein, Sao Paulo, Brazil. Electronic address: pedroming@gmail.com.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Azevedo
authors.affiliation: Biochemistry Department, University of Otago, Dunedin, New Zealand.
authors.forename: Tony R
authors.initials: TR
authors.lastname: Merriman
authors.affiliation: Biochemistry Department, University of Otago, Dunedin, New Zealand.
authors.forename: Ruth K
authors.initials: RK
authors.lastname: Topless
authors.affiliation: Green Lane Paediatric and Congenital Cardiac Services, Starship Children's Hospital, Auckland, New Zealand.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Wilson
authors.affiliation: University of Auckland, Tomaiora Māori Health Research Centre, Auckland, New Zealand.
authors.forename: Sue
authors.initials: S
authors.lastname: Crengle
authors.affiliation: Paediatrics, University of Auckland, Auckland, New Zealand.
authors.forename: Diana R
authors.initials: DR
authors.lastname: Lennon
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D009520:New Zealand; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012214:Rheumatic Heart Disease / Q000235:genetics*; D055815:Young Adult
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6
keywords: Interleukin-1 receptor antagonist (IL-1RA); Interleukin-6 (IL-6); Rheumatic fever; Rheumatic heart disease; cytotoxic T-lymphocyte associated protein 4 (CTLA4)