Association of angiotensin-converting enzyme gene polymorphisms with Crohn's disease in a Chinese Han population

Abstract

Objective: To investigate whether Angiotensin-converting enzyme (ACE) gene polymorphisms alter the susceptibility of a Chinese Han population to Crohn's disease (CD).

Methods: Blood samples were collected from patients with CD and from healthy control subjects for analyzing SNP rs4291 (promoter, A262T), SNP rs4343 (exon 16, A11860G), and rs4646994 (intron 16, Alu insertion/deletion). Allele and genotype frequencies were compared, and pairwise linkage disequilibrium and haplotypes were analyzed in patients with CD.

Results: Both rs4343 A/G and rs4646994 I/D allele frequencies differed significantly between patients with CD and control subjects (rs4343: OR=1.438, 95% CI=1.099-1.882, P=0.008; rs4646994: OR=1.559, 95% CI=1.191-2.039, P=0.001). There were also significant associations between the risk of CD and both rs4343 AA/(AG+GG) and rs4646994 II/(ID+DD) genotype frequencies (P=0.039 and P=0.019). The frequency of the G-D haplotype was significantly lower in patients with CD than control subjects (31.7% vs. 40.4%, P=0.010).

Conclusions: The results suggest that ACE rs4343G and rs4646994D alleles protect against CD, while rs4343AA and the I allele in the dominant genetic model are risk alleles for CD. The association between the G-D haplotype and CD was significant, suggesting a protective role in the pathogenesis of CD.

Keywords: ACE gene; Crohn’s disease; genetic polymorphisms.

Figure 1

Linkage disequilibrium analysis for rs4291, rs4343 and rs4646994 polymorphisms: The D’ values suggest that rs4646994 and rs4343 constitute a haplotype block. The two most frequent haplotypes, A-I and G-D, complemented each other at the two loci.