Effects of ACE rs4311C>T, rs4343A>G, rs4344A>G and rs4362C>T Polymorphisms on Angiotensin-Converting Enzyme Activity among Thai Subjects
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Abstract
Angiotensin-converting enzyme (ACE) metabolizes bradykinin and substance P. Variation in ACE gene alters ACE activity, consequently increasing or decreasing the bradykinin and substance P levels in the respiratory tract. This might explain the differences in incidence of cough due to ACE inhibitors according to ethnicity. This study aimed to investigate the influence of ACE polymorphisms (rs4311C>T, rs4343A>G, rs4344A>G and rs4362C>T) on serum ACE activity in Thai population. Allele frequencies of the SNPs from this study and those previously reported in other populations were also compared. Real-time polymerase chain reaction-based assay was used to detect ACE SNPs in genomic DNA. ACE activity was measured by a spectrophotometer. Among 100 Thai healthy volunteers, the frequencies of variant alleles for rs4311C>T, rs4343A>G, rs4344A>G and rs4362C>T were 0.28, 0.28, 0.29 and 0.33, respectively. The results showed significant differences in variant allele frequencies of rs4311C>T, rs4343A>G and rs4344A>G between Thai and other populations (p<0.05). Significant increases in median ACE activity were observed in subjects with homozygous variant alleles of the following SNPs compared to those with homozygous wild-type allele: rs4311C>T (52 vs. 26 U/L, p=0.001), rs4343A>G (52 vs. 26 U/L, p=0.000), rs4344A>G (52 vs. 26 U/L, p=0.003) and rs4362C>T (48 vs. 24 U/L, p=0.001). In conclusion, our study demonstrated the effects of ACE (rs4311C>T, rs4343A>G, rs4344A>G and rs4362C>T) polymorphisms on ACE activity in Thai subjects. Further studies should be performed to elucidate the relationships between these ACE polymorphisms and incidence of cough related to ACE inhibitors in Thai population.
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References
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