Abstract
Genetic mechanisms involved in the susceptibility to salt sensitivity have not been completely clarified. This study aimed to comprehensively examine the association between genetic variants in the cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG/PRKG) genes and blood pressure (BP) responses to dietary sodium intervention in a Chinese population. A 7-day low-sodium intervention followed by a 7-day high-sodium intervention was conducted among 1906 Han participants from rural areas of northern China. Nine BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the additive association of 213 tag single-nucleotide polymorphisms (SNPs) in two PRKG genes (PRKG1 and PRKG2) with salt sensitivity phenotypes. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing. Mean systolic BP response to low-sodium intervention significantly decreased with the number of minor T allele of marker rs10997916 in PRKG1 (P = 2.4 × 10−5). Mean systolic BP responses (95% confidence interval) among those with genotypes CC, CT, and TT were −5.6 (−6.0, −5.3), −3.7 (−4.7, −2.8), and −1.3 (−4.6, 2.0) mmHg, respectively, during the low-sodium intervention. Gene-based analyses demonstrated that PRKG1 was significantly associated with systolic BP response to low-sodium intervention (P = 1.2 × 10−3), whereas PRKG2 was nominally significantly associated with diastolic BP responses to high-sodium intervention (P = 2.6 × 10−2). The current study suggested a significant association of genetic variants in the PRKG genes with variation of BP response to dietary sodium intake in Han Chinese population. These novel findings merit further replication in future.
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Acknowledgements
This study is supported by the National Natural Science Foundation of China (GRANT NO. 91439202, 81570386, 91643208, 81773537, 81600332) and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (grants no. 2017-I2M-1–004, 2016-I2M-2–001, and 2016-I2M-1-011). The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is supported by a cooperative agreement project grant (U01HL072507, R01HL087263, and R01HL090682) from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
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41371_2018_99_MOESM5_ESM.doc
Supplementary Table 5. P values of single SNP association analysis of the 213 SNPs in PRKG1 and PRKG2 with BP responses to dietary sodium intervention.
41371_2018_99_MOESM6_ESM.doc
Supplementary Table 6. Gene-based associations of PRKG1 and PRKG2 with BP responses to dietary sodium intervention after removing the lead marker.
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Han, C., Hu, Z., Liu, F. et al. Genetic variants of cGMP-dependent protein kinase genes and salt sensitivity of blood pressure: the GenSalt study. J Hum Hypertens 33, 62–68 (2019). https://doi.org/10.1038/s41371-018-0099-1
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DOI: https://doi.org/10.1038/s41371-018-0099-1