深圳龙华区妊娠期高血压孕妇血清中PAPP-A水平及其基因rs7020782 A/C位点多态性分析

Analysis of PAPP-A level in serum and polymorphism of its gene rs7020782 A/C locus in pregnant women with hypertension during pregnancy in Longhua District

目的了解深圳龙华区不同严重程度妊娠期高血压(GH)孕妇血清中妊娠相关血浆蛋白-A(PAPP-A)水平及其基因(PAPP-A)rs7020782 A/C位点单核苷酸多态性(SNP)与该地区GH发病的易感性。方法选择2019年3月至2021年2月在深圳市龙华区人民医院确诊GH孕妇279例(GH组),年龄24~43岁,平均年龄30.85岁;孕周21~35周,平均孕周28.06周。同期健康非GH孕妇108例(对照组),年龄23~45岁,平均年龄31.07岁;孕周20~34周,平均孕周27.54周。采用酶联免疫吸附分析(ELISA)法检测PAPP-A水平,同时采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)法检测PAPP-A rs7020782 A/C位点SNP。结果 GH组PAPP-A水平为(8.92±3.15) mIU/L,明显高于对照组[(5.41±1.73) mIU/L],差异有统计学意义(t=6.054 8,P <0.05);其中重度组PAPP-A水平为(13.23±4.15) mIU/L,明显高于中度组[(9.24±2.51) mIU/L],而中度组明显高于轻度组[(6.58±2.07) mIU/L],不同组别之间差异有统计学意义(F=10.514 3,P <0.05)。GH组PAPP-A rs7020782 A/C位点CC基因型和C等位基因频率分别为30.47%和48.75%,明显高于对照组(9.26%和28.24%),差异有统计学意义(P <0.05);且CC基因型和C等位基因患GH的相对风险增加[比值比(OR)=2.836,95%可信区间(CI)1.725~4.713和OR=2.016,95%CI 1.632~3.548]。携带PAPP-A rs7020782 A/C位点CC基因型GH孕妇血清中PAPP-A水平为(11.98±3.76) mIU/L,明显高于AA和AC基因型[(7.31±2.30) mIU/L和(7.80±2.54) mIU/L],差异有统计学意义(P <0.05);但AA和AC基因型之间差异无统计学意义(P> 0.05)。结论 GH孕妇血清中PAPP-A水平明显升高,且随病情加重而升高。同时PAPP-A rs7020782 A/C位点呈多态性分布,与深圳龙华区GH发病存在一定关系,其中CC基因型患GH的相对风险增加,可能是该地区GH发病的危险易感基因之一。

Objective To investigate serum levels of pregnancy-associated plasma protein-A(PAPP-A) and single nucleotide polymorphism(SNP) of its gene(PAPP-A) rs7020782 A/C locus in pregnant women with different severity of gestational hyper-tension(GH) in Longhua District of Shenzhen and the susceptibility of GH in the area. Methods From March 2019 to February 2021, 279 pregnant women with GH(GH group) were enrolled, aged 24-43 years old with mean age of 30.85 years old;gestational age was 21-35 weeks with mean gestational age of 28.06 weeks. In the same period, 108 healthy non-GH pregnant women were set as control group, which aged 23-45 years old with mean age of 31.07 years old;gestational age was 20-34 weeks with mean gestational age of 27.54 weeks. The enzyme-linked immunosorbent assay(ELISA) was used to detect PAPPA level, and polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method was used to detect SNP at rs7020782 A/C locus of PAPP-A. Results The level of PAPP-A in GH group[(8.92 ± 3.15) m IU/L] was significantly higher than that in control group[(5.41 ± 1.73) mIU/L], and the difference was statistically significant(t = 6.054 8, P < 0.05).The level of PAPP-A in severe group[(13.23 ± 4.15) mIU/L] was significantly higher than that in moderate group[(9.24 ±2.51) mIU/L], while PAPP-A level in moderate group was significantly higher than that in mild group[(6.58 ± 2.07) mIU/L], and the differences between different groups were statistically significant(F = 10.514 3, P < 0.05). The CC genotype and C allele frequencies of PAPP-A rs7020782 A/C loci in GH group were 30.47 % and 48.75 %, respectively, which were significantly higher than those in control group(9.26 % and 28.24 %), and the differences were statistically significant(P < 0.05). The CC genotype and C allele showed increased relative risk of GH[odds ratio(OR) = 2.836, 95 % confidence interval(CI) 1.725-4.713 and OR = 2.016,95 % CI 1.632-3.548]. The serum level of PAPP-A in pregnant women carrying PAPP-A rs7020782 A/C locus CC genotype was(11.98 ± 3.76) mIU/L, which was significantly higher than that of AA and AC genotypes[(7.31 ± 2.30) mIU/L and(7.80 ± 2.54) mIU/L], and the differences were statistically significant(P < 0.05). However, there was no significant difference between AA and AC genotypes(P > 0.05). Conclusion It is demonstrated that the level of PAPP-A in serum of GH pregnant women increased significantly, and increased with severity of disease. Meanwhile, rs7020782 A/C locus of PAPP-A is polymorphic, which has certain relationship with the incidence of GH in Longhua District. The CC genotype has an increased relative risk of GH, which may be one of the risk susceptibility genes for GH in the area.