抗酸菌症
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概要

Genetic Variation at the DNASE I Locus in an Australian Cohort of SLE Patients

Audrey A Margery-Muir, John D Wetherall and David M Groth

Objective: DNASE I serum concentrations and activity, as well as sequence mutations have been implicated in the pathology of systemic lupus erythematosus (SLE). This study was undertaken to assess the serum DNASE I concentrations and assess the DNASE I sequence variation in a cohort of SLE patients and controls.

Methods: DNASE I serum concentrations were assayed in 56 SLE patients and 33 age and sex matched controls. All SLE patients and controls were genotyped for exomic alleles at the DNASE I locus and for the variable number tandem repeat alleles present in intron 4 (VNTR - HumDN1).

Results: Skewed DNASE I protein concentration distributions were observed with the mean value for SLE patients being 44.2 U/mL compared to 56.4 U/mL in controls (NS). No sample tested negative for DNASE I protein. Only two of the previously reported six exomic alleles (DNASE*1, DNASE*2) were identified, together with four VNTR alleles (three-six repeats). Both loci manifested Hardy-Weinberg equilibrium. Linkage disequilibrium was observed between exomic alleles and the VNTR alleles, especially between DNASE I* and 4 repeat VNTR (HumDN1) allele. No significant associations were observed between DNASE I concentrations and genotypes. Estimations of haplotype frequencies showed similar distributions for both SLE and the control cohorts, although it was noted that haplotypes containing DNASE*2 had an elevated frequency of longer VNTR alleles than did DNASE*1.

A meta-study of DNASE I exomic allelic frequencies showed similar frequencies to those obtained in other populations. For the VNTR locus, the longer alleles (five and six repeats) were more frequent, although there was no difference between SLE patients and controls.

Conclusion: This study does not support the hypothesis that specific two locus DNASE I genotypes predispose to SLE in the Western Australian cohort.