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Alpha₁-antitrypsin deficiency-related alleles Z and S and the risk of Wegener's granulomatosis.

Publication ,  Journal Article
Mahr, AD; Edberg, JC; Stone, JH; Hoffman, GS; St Clair, EW; Specks, U; Dellaripa, PF; Seo, P; Spiera, RF; Rouhani, FN; Brantly, ML; Merkel, PA
Published in: Arthritis Rheum
December 2010

OBJECTIVE: Deficiency of α(1) -antitrypsin (α(1) AT) may be a determinant of susceptibility to Wegener's granulomatosis (WG). Several previous, mainly small, case-control studies have shown that 5-27% of patients with WG carried the α(1) AT deficiency Z allele. It is not clear whether the S allele, the other major α(1) AT deficiency variant, is associated with WG. This study investigated the relationship of the α(1) AT deficiency Z and S alleles with the risk of developing WG in a large cohort. METHODS: We studied the distribution of the α(1) AT deficiency alleles Z and S in 433 unrelated Caucasian patients with WG and 421 ethnically matched controls. Genotyping was performed using an allele discrimination assay. Results were compared between cases and controls using exact statistical methods. RESULTS: Among the patients with WG, the allele carriage frequencies of Z and S were 7.4% and 11.5%, respectively. The frequencies of the 6 possible genotypes differed in a statistically significant manner between cases and controls (P = 0.01). The general genetic 2-parameter codominant model provided the best fit to the data. Compared with the normal MM genotype, the odds ratio (OR) for MZ or MS genotypes was 1.47 (95% confidence interval [95% CI] 0.98-2.22), and the OR for ZZ, SS, or SZ genotypes was 14.58 (95% CI 2.33-∞). ORs of similar direction and magnitude were observed within the restricted cohorts that excluded cases and controls carrying ≥1 Z or ≥1 S allele. CONCLUSION: Both Z and S alleles display associations with risk of WG in a codominant genetic pattern. These findings strengthen the evidence of a causal link between α(1) AT deficiency and susceptibility to WG.

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Published In

Arthritis Rheum

DOI

EISSN

1529-0131

Publication Date

December 2010

Volume

62

Issue

12

Start / End Page

3760 / 3767

Location

United States

Related Subject Headings

  • alpha 1-Antitrypsin
  • White People
  • Risk Factors
  • Middle Aged
  • Male
  • Humans
  • Granulomatosis with Polyangiitis
  • Genotype
  • Genetic Predisposition to Disease
  • Gene Frequency
 

Citation

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Mahr, A. D., Edberg, J. C., Stone, J. H., Hoffman, G. S., St Clair, E. W., Specks, U., … Merkel, P. A. (2010). Alpha₁-antitrypsin deficiency-related alleles Z and S and the risk of Wegener's granulomatosis. Arthritis Rheum, 62(12), 3760–3767. https://doi.org/10.1002/art.27742
Mahr, Alfred D., Jeffrey C. Edberg, John H. Stone, Gary S. Hoffman, E William St Clair, Ulrich Specks, Paul F. Dellaripa, et al. “Alpha₁-antitrypsin deficiency-related alleles Z and S and the risk of Wegener's granulomatosis.Arthritis Rheum 62, no. 12 (December 2010): 3760–67. https://doi.org/10.1002/art.27742.
Mahr AD, Edberg JC, Stone JH, Hoffman GS, St Clair EW, Specks U, et al. Alpha₁-antitrypsin deficiency-related alleles Z and S and the risk of Wegener's granulomatosis. Arthritis Rheum. 2010 Dec;62(12):3760–7.
Mahr, Alfred D., et al. “Alpha₁-antitrypsin deficiency-related alleles Z and S and the risk of Wegener's granulomatosis.Arthritis Rheum, vol. 62, no. 12, Dec. 2010, pp. 3760–67. Pubmed, doi:10.1002/art.27742.
Mahr AD, Edberg JC, Stone JH, Hoffman GS, St Clair EW, Specks U, Dellaripa PF, Seo P, Spiera RF, Rouhani FN, Brantly ML, Merkel PA. Alpha₁-antitrypsin deficiency-related alleles Z and S and the risk of Wegener's granulomatosis. Arthritis Rheum. 2010 Dec;62(12):3760–3767.
Journal cover image

Published In

Arthritis Rheum

DOI

EISSN

1529-0131

Publication Date

December 2010

Volume

62

Issue

12

Start / End Page

3760 / 3767

Location

United States

Related Subject Headings

  • alpha 1-Antitrypsin
  • White People
  • Risk Factors
  • Middle Aged
  • Male
  • Humans
  • Granulomatosis with Polyangiitis
  • Genotype
  • Genetic Predisposition to Disease
  • Gene Frequency