Impact of interaction of cigarette smoking with angiotensin-converting enzyme polymorphisms on end-stage renal disease risk in a Han Chinese population

Abstract

Background: Several polymorphisms in the angiotensin-converting enzyme (ACE) and ACE2 genes are associated with the development of end-stage renal disease (ESRD). Certain genetic polymorphisms may modify the deleterious effects of environmental factors such as cigarette smoking and may also modify the inherited risk. We investigated the association of six ACE and ACE2 polymorphisms with ESRD to determine whether a relationship exists between gene-smoking interactions and ESRD. Materials and methods:We performed a case-control association study and genotyped 683 ESRD patients and 653 healthy controls. All subjects were genotyped for ACE (I/D, G2350A and A-240T) and ACE2 (G8790A, A1075G and G16854C) gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Significant associations were observed between ACE I/D and G2350A polymorphisms and ESRD. There was no difference in ACE2 genotype distribution between ESRD patients and healthy controls. Haplotype analysis showed that DAA and DAT haplotypes were risk factors for ESRD. Moreover, a gene-environment interaction was observed between ACE I/D polymorphism and cigarette smoking. Conclusion: ACE I/D and ACE G2350A polymorphisms were associated with the development of ESRD. The interaction between ACE I/D polymorphism and smoking is also associated with an enhanced risk of ESRD.

Smoking has no impact on survival and it is not associated with ACE gene I/D polymorphism in hemodialysis patients

“…Our cohort included only patients of Caucasian origin, and therefore our results might be difficult to generalize to patients of other races. ACE I and D allele frequencies might well be different in other races, as was shown among Han Chinese ESRD patients in a recent report by Yang et al 19 …”

“…Furthermore, the authors claimed that interaction of the gene polymorphism and smoking can enhance the development of ESRD because smokers with the D/D genotype followed by the I/D genotype showed inferior outcome for disease progression compared to patients with the I/I genotype. 19 In contrast, in an earlier study, the authors did not find any association between ACE gene I/D polymorphism and smoking status. 20 Despite a considerable amount of evidence about the harmful effect of smoking on the progression of renal disease of various etiologies and its impact on mortality, there are still conflicting data about the association between smoking and survival in patients on hemodialysis.…”

Association of ACE2 polymorphisms with susceptibility to essential hypertension and dyslipidemia in Xinjiang, China

“…The possible mechanism would be related to changes in quantity and function of ACE2 mutant protein owing to ACE2 polymorphism related amino acid substitutions(e.g., 1075A/G(rs1978124), 8790G/A (rs2285666) and 16854G/C(rs4646142), etc. [ 25 , 47 ]), which might be involved in the posttranscriptional regulation via microRNA, the mRNA splicing efficiency (e.g., intron splicing enhancer or silencer element) and mRNA stability (e.g., conformation) of ACE2, at least partly confirmed by recent research that the changes of ACE2 expression was in protein level rather than mRNA level in mice [ 48 ], and microRNA might regulate RAAS activity via by altering the interaction between microRNA and mRNA of targeted gene [ 44 ]. In addition, ACE2 SNP rs4830542 was found to be located in the 3’-UTR region while the other 13 ACE2 SNPs (e.g., rs4646188) were in intron.…”

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Susceptibility to Osteoarthritis of the Knee: A Case-Control Study and Meta-Analysis

“…Genomic DNA was extracted from peripheral blood samples using standard procedures for proteinase K (Invitrogen, Carlsbad, CA, USA) digestion and phenol/chloroform extraction. ACE I/D polymorphisms were screened using the polymerase chain reaction (PCR) according to a previously described protocol [ 46 ]. The primers were also described previously [ 47 ].…”