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Objective: To investigate the effects of environmental risk factors and two SNPs and haplotypes structures of PRKG1 gene with blood salt-sensitive among essential hypertension after acute salt load test.This research will contribute significantly to knowledge about screening the environmental and genetic biomarkers, and is useful for predicting salt-sensitive hypertensive and development of targeted intervention for the prevention.Method: Three hundreds and forty two essential hypertensives were recruit in a case-only study, a modified Sullirans acute salt load method is conducted to identify the salt-sensitivity (SS) and salt-resistant (SR).Medical history and lifestyle risk factors are obtained by questionnaire, while blood pressure and weight are measured by physical examination, and blood and urine specimens are collected to test the biochemical indicators.The daily sodium intake of individuals is assessed by food frequecy questionnaire and 24-hour urinary sodium excretion.We extracted genome DNA in peripheral blood leukocytes and used Sequenom Mass ARRAY Platform (San Diego, Calif) for genotyping of PRKG1 gene SNPs (SNP1: rs7897633;SNP2: rs1904694).We applied statistical software SPSS17.0, multifactor dimensionality reduction method 1.1.0 and haploview 4.1 to do the analyses.Results: There were 63 salt sensitivity subjects in 342 essential hypertension, accounting for 18.4% of the total.Age and 24-hour urine sodium concentration were the risk factors associated with salt sensitivity.The genotype distributions of PRKG1 gene obeyed the Hardy-Weinbergs equilibrium (P >0.05) in either SS or SR groups.The results of the logistic regression model showed that subjects carrying SNP1-AA genotype and SNP2-GG genotypes had 2.831-fold (95%CI: 1.208-6.633) and 3.499-fold (95%CI: 1.544-7.932) risks to be salt sensitive hypertension had, respectively.There was no significant interaction between SNP1 and SNP2, while there was moderate strength interaction among the two SNPs with 24-hour urine sodium concentration associated with salt-sensitivity.Haplotype analysis showed that there were significant frequency differences between SS and SR groups in H1 (SNP1-C/SNP2-A) and H2 (SNP1-A/SNP2-G).Haplotype H 1 had 0.562-fold (95%CI: 0.375-0.843) decreased risk for salt-sensitive hypertension;whereas, haplotype H2 had 1.784-fold (95%CI: 1.200-2.651) increased risk for salt-sensitive hypertension.Conclusion: Age and 24-hour urine sodium concentration are the risk environmental factors associated with salt sensitivity of essential hypertension.Genotypes of SNP1-AA, SNP2-GG and haplotype AG of PRKG1 gene were risk factors for salt-sensitivity in essential hypertension.There was moderate strength interaction among the two SNPs with 24-hour urine sodium concentration associated with salt-sensitivity.