Analysis of A1166C Polymorphism in Type I Receptor for Angiotensin II Gene with Pregnancy Induced Hypertension(PIH) in Korean Women / 대한주산의학회잡지

ABSTRACT

BACKGROUND/AIM: Recent studies have suggested an association between genetic background of renin-angiotensin(RA) system and the pathogenesis of pregnancy induced hypertension(PIH). Even though various single nucleotide polymorphism(SNP) such as M235T, T174M polymorphism in angiotensinogen gene(AGT) and I/D polymorphism in angiotensin I-converting enzyme gene(ACE) have been studied extensively among essential hypertension and PIH in various population, its association was still inconclusive. Previous studies within Korean PIH patients also revealed that M235T or T174M single nucleotide polymorphism in AGT gene or I/D polymorphism in ACE gene were not linked tightly with PIH. However, recent studies on angiotensin II type I receptor(AT1) polymorphism A1166C with PIH in Polish or in Chinese suggested its possible correlations to a pathogenesis of PIH. Thus the aim of the present study was to determine the frequency of genotypes of A1166C mu-tation in women with PIH and to establish the role of this polymorphism on the susceptibility to the PIH development. PATIENTS AND METHODS: We have analysed 121 women with PIH and 98 healthy normotensive gravid women as a control. Genomic DNA was used for PCR. To genotype the A1166C polymorphism in angiotensin II receptor(AT1) gene, primers(sense 5'-CGA CTA CTG CTT AGC ATA-3', antisense 5'-GCA CCA TGT TTT GAG GTT-3') were employed to make 546bp PCR product. There was an initial denaturation at 94degrees C 5 minutes, followed by 30 cycles of one minute at 94degrees C, one minute at 58degrees C, and two minutes at 7degrees C. A 546bp PCR product was further digested with DdeI for 2 hour at 37degrees C and analysed through 2% agarose gel electrophoresis to determine genotype. Allele C1166 yielded 435bp, 111bp fragment and allele A1166 yielded intact 546 bp fragment RESULTS: We found that frequency of genotype A1166/C1166 and A1166/A1166 in PIH were 9.9% (12) and 90.1%(109), while in controls were 17.3%(17) and 82.7%(81). There was no statistical significance between development of PIH and A1166C polymorphism in type I receptor for Angiotensin II. Homozygous mutated genotype(C1166/C1166) was not detected in this study. CONCLUSION: Our results found no possible correlation of A1166C polymorphism in angiotensin II receptor(AT1) with PIH in Korean and found that allele C might behave as a protective factor rather than as a risk factor in the pathogenesis of PIH. We suggest a large-scale study to evaluate relevance to this polymorphism for PIH.