Introduction: Association studies with single nucleotide polymorphisms (SNPs) have been contradictory. Haplotypes may be more helpful. With gene sequencing, all SNPs can be found for construction of haplotypes.
Methods: The ACE gene was sequenced in four healthy Chinese subjects and 20 patients with IgA nephropathy (IgAN) to observe if differences exist among SNPs and haplotypes. 20 patients on angiotensin 1-converting enzyme inhibitor/angiotensin receptor antagonist (ACEI/ATRA) therapy were then compared with another 20 patients not treated with ACEI /ATRA to determine their renal outcome in response to ACEI/ATRA therapy and whether their genetic profile of ACE gene could play a role in determining their outcome to ACEI /ATRA therapy and progression to end-stage renal failure (ESRF).
Results: IgAN patients had 53 variants, of which 17 were unique, whereas normal subjects had 38 variants, of which two were unique (p less than 0.005). No unique variant was a significant risk factor for IgAN. Significant genotype and allele frequency differences in five variants were observed between IgAN patients with renal impairment and those with ESRF (p less than 0.02).
Conclusion: Our data suggests that at least in the ACE gene, haplotyping SNPs within a single gene seems to have no added advantage over genotyping the individual component SNPs. The D allele and haplotype 3 confer an adverse prognosis, while the I allele and haplotype 5 appear to be renoprotective. The data suggests that genotypes of the ACE gene are linked to certain haplotypes, which could influence IgAN patients' response to ACEI/ATRA therapy.