Association Of Single Nucleotide Polymorphisms In The Apelin-APJ System With Hypertension And Hypertensive Vascular Damage

ObjectivesThe aim of this study was to explore the association of single nucleotidepolymorphisms (SNPs) in the apelin gene and its receptor APJ gene with hypertensionand hypertensive fundus artery stenosis or reduced arterial elasticity in a Chinesepopulation from the coastal area of Fujian Province.MethodsTotal of1031subjects,398men and633women, were enrolled in this studybased on a cross-sectional survey in Fujian coastal area in2011. All subjects, whowere divided into hypertension group and control group, were given physicalexamination, laboratory test, fundus photography and cardiovascular screening. Fivesingle nucleotide polymorphisms (SNPs) were evaluated using Taqman@MGB probe,including apelin rs3115757, apelin rs56204867, apelin rs3761581, APJ rs7119375andAPJ rs9943582. Central retinal artery diameter (CRAE) was measured by fundusphotography. Brachial ankle pulse wave velocity (baPWV) was measured using thePWV device.Results1. The allele-frequency distributions for3SNPs in apelin gene were differentbetween the hypertension group and control group in men (rs3115757-C:53.8%vs.15.1%, rs56204867-C:48.4%vs.27.7%, rs3761581-A:72.8%vs.53.3%, all P<0.05).The allele-frequency distributions for2SNPs in APJ gene were the same(rs7119375-A:29.2%vs.31.3%, rs9943582-T:33.2%vs.34.4%, P>0.05) betweentwo groups in men. The allele-frequency distributions for all5SNPs were the samebetween two groups in women (P>0.05).2. After adjustment for age, body mass index and fasting blood glucose, the subjects with the mutant allele of rs3115757-C, rs56204867-C or rs3761581-A weremore likely to develop hypertension in both gender [odds ratio (OR)=6.341,2.410and1.949respectively for men, OR=2.069,2.052and2.000, respectively for women,all P<0.05].3. The best genes interaction model of hypertension was apelin rs3761581-apelin rs3115757-APJ rs7119375model in both gender.4. The male subjects with mutant allele of apelin rs3115757-C had asignificantly higher baPWV than those with wild allele after adjusting for age(P<0.05). The female subjects with mutant allele of apelin rs56204867-C had anincreased risk of developing abnormal baPWV (OR=2.087, P <0.05).5. The CRAE level was significantly increased in male subjects who carryingthe mutant allele of APJ rs9943582-T compared with those subjects who carrying thewild allele after adjusting for age (P<0.05). The mutant allele of APJ rs9943582-Twas associated with a less risk of developing fundus artery stenosis in males withhypertension (OR=0.108, P<0.05).ConclusionThe apelin SNPs rs3115757, rs56204867, rs3761581and APJ SNP rs7119375were associated with hypertension. The apelin SNP rs56204867was associated withreduced arterial elasticity in female subjects with hypertension. The APJ SNPrs9943582was associated with fundus artery stenosis in male subjects withhypertension. The SNPs in apelin-APJ pathway may be associated with hypertensionand hypertensive vascular damage in a Chinese population from the coastal area ofFujian Province.