Soluble guanylate cyclase contribute genetic susceptibility to essential hypertension in the Han Chinese population

Yan Chen, Lijun Zhu, Zhengmei Fang, Yuelong Jin, Chong Shen, Yingshui Yao, Chengchao Zhou


Background: Animal study found that soluble guanylate cyclase (sGC) plays an important role in development of hypertension (HT) by affecting the NO-sGC-CGMP signaling pathway. This study aims to evaluate the association of sGC with essential hypertension (EH) in the Han Chinese population.
Methods: This case-control study included 2,012 hypertensive cases and 2,210 controls, and 6 tagging single nucleotide polymorphisms (SNPs) were selected (rs3806777, rs3806782, rs3796576 and rs7698460 in GUCY1A3, as well as rs2229202 and rs1459853 in GUCY1B3). Then the association of the six SNPs with EH was further evaluated in this study.
Results: The results indicated that the A/A genotype of rs1459853 in GUCY1B3 was associated with higher HT risk, and the odds ratio (OR) of its recessive model was 1.191 (P=0.044). After adjusting for covariates, the association was still significant. Further stratification analyses showed that rs1459853 in non- drinking subjects and rs7698460 in women were associated with EH. In the follow-up study, rs1459853 were related to increased HT risk in men and smoker subjects. In adolescents, rs2229202 that in GUCY1B3 had significant association with prehypertension (Pre-HT), HT, and prehypertension with hypertension (Pre-HT + HT). After adjusted for covariates, the association was remaining significant. And in girls, rs3806782 was significantly connected with HT and Pre-HT + HT.
Conclusions: Overall, our findings suggest that sGC may contribute to the genetic susceptibility to EH, and it was validated for the first time in adolescents.