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南非孕妇 p53 Pro72Arg(rs1042522)基因分型的母婴 HIV 感染、BMI 和 NOx 空气污染暴露对出生结局的影响。

Effect of maternal HIV infection, BMI and NOx air pollution exposure on birth outcomes in South African pregnant women genotyped for the p53 Pro72Arg (rs1042522).

机构信息

Discipline of Medical Biochemistry and Chemical Pathology, Howard College Campus, University of KwaZulu-Natal, Durban, South Africa.

Discipline of Occupational and Environmental Health, Howard College Campus, University of KwaZulu-Natal, Durban, South Africa.

出版信息

Int J Immunogenet. 2020 Oct;47(5):414-429. doi: 10.1111/iji.12481. Epub 2020 Feb 20.

Abstract

Tumour suppressor protein, p53, plays a role in modulating innate immune responses, DNA repair, cell cycle arrest, senescence and apoptosis. Maternal nitrogen oxide (NOx) air pollution exposure, body mass index (BMI), human immunodeficiency virus (HIV) infection and p53 Pro72Arg (rs1042522) affect foetal growth. We investigated whether the aforementioned factors influence birth outcomes in a South African population. Pregnant women (n = 300; HIV -ve = 194 and HIV +ve = 106) were genotyped for the p53 rs1042522 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and further stratified based on HIV status, infants' birthweight (BW; NBW: normal BW [>2,500 g] and LBW: low BW [<2,500 g]) and gestational age (GA; NGA: normal GA [>37 weeks] and PTB: preterm birth [≤37 weeks]). A land use regression model was developed to characterize maternal NOx exposure. Pearson's correlation and multivariate regression analysis statistical tests were used to determine the effect of rs1042522 genotyped pregnant women's BMI and NOx exposure on maternal blood pressure and haemoglobin and iron levels, and infants' anthropometric measurements and Appearance Pulse Grimace Activity and Respiration (APGAR) scores. The prevalence of LBW and PTB was 14.7% and 18.7%, respectively. The LBW group had a higher frequency of the variant Arg-allele versus NBW group (47.7% vs. 31.4%, p = .0046, OR = 2.0, 95% CI = 1.26-3.17). No association was observed between NGA and PTB groups. A significant association between BMI and systolic blood pressure (r = .50, p = .00; B = 0.76, p = .002) and birth length (r = -.28, p = .01; B = -0.107, p = .011), and NOx and birth length (r = -.26, p = .08; B = -0.191, p = .046) and birthweight (B = -8.87, p = .048) was observed in HIV-infected mothers with the variant Pro/Arg + Arg/Arg genotypes. Mothers from the LBW group with the variant genotypes displayed an association between NOx and diastolic blood pressure (r = .58, p = .04), blood iron levels (r = -.60, p = .04; B = -0.204, p = .004), APGAR scores at 1 min (r = -.86, p = .00; B = -0.101, p = .003) and 5 min (r = -.75, p = .01) and birth length (r = -.61, p = .04), and BMI and diastolic blood pressure (r = .72, p = .01). In the PTB group, maternal variant genotypes and NOx were associated with blood haemoglobin levels (B = -0.132, p = .045) and APGAR scores at 1 min (B = -0.161, p = .045) and 5 min (B = -0.147, p = .043). Maternal rs1042522 Arg-allele, HIV infection, BMI and NOx exposure collectively play a role in lowering blood iron levels, gestational hypertension and LBW outcomes.

摘要

抑癌蛋白 p53 在调节先天免疫反应、DNA 修复、细胞周期阻滞、衰老和凋亡方面发挥作用。母体氮氧化物(NOx)空气污染暴露、体重指数(BMI)、人类免疫缺陷病毒(HIV)感染和 p53 Pro72Arg(rs1042522)影响胎儿生长。我们研究了上述因素是否会影响南非人群的出生结局。使用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对 300 名孕妇(HIV-ve=194,HIV+ve=106)进行 p53 rs1042522 基因分型,并根据 HIV 状态、婴儿出生体重(NBW:正常 BW[>2500g]和 LBW:低 BW [<2500g])和胎龄(NGA:正常 GA[>37 周]和 PTB:早产[≤37 周])进一步分层。建立了一个土地利用回归模型来描述母体 NOx 暴露情况。使用 Pearson 相关和多元回归分析统计检验来确定 rs1042522 基因型孕妇的 BMI 和 NOx 暴露对母体血压和血红蛋白及铁水平的影响,以及婴儿的人体测量学测量值和Appearance Pulse Grimace Activity and Respiration(APGAR)评分。LBW 和 PTB 的发生率分别为 14.7%和 18.7%。LBW 组的变异型 Arg 等位基因频率高于 NBW 组(47.7% vs. 31.4%,p=0.0046,OR=2.0,95%CI=1.26-3.17)。NGA 和 PTB 组之间没有关联。BMI 与收缩压(r=0.50,p=0.00;B=0.76,p=0.002)和出生长度(r=-0.28,p=0.01;B=-0.107,p=0.011)以及 NOx 与出生长度(r=-0.26,p=0.08;B=-0.191,p=0.046)和出生体重(B=-8.87,p=0.048)之间存在显著相关性,在感染 HIV 的母亲中具有 Pro/Arg+Arg/Arg 变异基因型。具有变异基因型的 LBW 组母亲的 NOx 与舒张压(r=0.58,p=0.04)、血液铁水平(r=-0.60,p=0.04;B=-0.204,p=0.004)、1 分钟 APGAR 评分(r=-0.86,p=0.00;B=-0.101,p=0.003)和 5 分钟 APGAR 评分(r=-0.75,p=0.01)和出生长度(r=-0.61,p=0.04)之间存在关联,BMI 与舒张压(r=0.72,p=0.01)之间存在关联。在 PTB 组中,母体变异基因型和 NOx 与血液血红蛋白水平(B=-0.132,p=0.045)和 1 分钟 APGAR 评分(B=-0.161,p=0.045)和 5 分钟 APGAR 评分(B=-0.147,p=0.043)相关。母体 rs1042522 Arg 等位基因、HIV 感染、BMI 和 NOx 暴露共同导致血液铁水平降低、妊娠高血压和 LBW 结局。

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