Department of Clinical Epidemiology, Children's Hospital of Fudan University, Shanghai, China.
J Hum Genet. 2013 May;58(5):293-7. doi: 10.1038/jhg.2013.18. Epub 2013 Mar 14.
The objective of this study was to investigate the overall contribution of genetic and environmental effects on poor response to hepatitis B virus (HBV) vaccination in Chinese infants. One-year-old healthy twins were recruited from child-care settings. Parental factors, neonates' condition at birth, postnatal infant feeding history and growth measurements during the 12 months were investigated by conducting an interview and checking the medical records. HBV-related markers were examined at 1 year of age. Heritability of surface antibody to HBV (anti-HBs) concentrations (ordinal variable) among twins was estimated using MX software. The role of perinatal environmental factors on poor vaccine response (anti-HBs<100 mIU ml(-1)) was analyzed using XTGEE (fit population-averaged panel-data models by using GEE) programs. Overall, 172 out of 225 recruited twin pairs were analyzed for heritability, including 82 pairs (47.67%) of monozygotic twins and 90 pairs of dizygotic twins, which consisted 43 pairs of (25.0%) opposite sex twins, 29 pairs of male twins and 18 pairs of female twins. Seventy-one (19.9%) of 370 twins showed poor responses to HBV vaccine. An additive genetic (0.91 of the variance)-random environmental (0.09 of the variance)-model best fit the variation of anti-HBs response. Risk factor analysis showed that with a smoking father and low birth weight, the infants were associated with an increased risk of poor response to HBV vaccination (odds ratio (OR)=4.50, 95% confidence interval (CI): 2.52-8.03 and OR=2.55, 95% CI: 1.33-4.87, respectively). Higher Apgar score and gaining more body weight in the first year of life reduced this risk. Genetic factors have a dominant role in determining infant HBV vaccination responses (91%) compared with perinatal environmental factors.
本研究旨在探讨遗传和环境因素对中国婴儿乙型肝炎病毒 (HBV) 疫苗接种无应答的综合影响。从儿童保健机构招募 1 岁的健康双胞胎。通过访谈和查阅病历,调查父母因素、新生儿出生时的情况、产后婴儿喂养史和 12 个月内的生长测量情况。在 1 岁时检查 HBV 相关标志物。使用 MX 软件估计双胞胎表面抗体抗 HBV(抗-HBs)浓度(有序变量)的遗传力。使用 XTGEE(通过 GEE 拟合人群平均面板数据模型)程序分析围产期环境因素对疫苗无应答(抗-HBs<100 mIU/ml)的作用。总体而言,对 225 对招募的双胞胎中的 172 对进行了遗传力分析,包括 82 对(47.67%)同卵双胞胎和 90 对异卵双胞胎,其中包括 43 对(25.0%)异性双胞胎、29 对男性双胞胎和 18 对女性双胞胎。370 对双胞胎中有 71 对(19.9%)对 HBV 疫苗反应不佳。加性遗传(方差的 0.91)-随机环境(方差的 0.09)-模型最适合抗-HBs 反应的变异。风险因素分析表明,父亲吸烟和低出生体重使婴儿对 HBV 疫苗接种无应答的风险增加(比值比(OR)=4.50,95%置信区间(CI):2.52-8.03 和 OR=2.55,95%CI:1.33-4.87)。出生后第一年获得更高的阿普加评分和增加更多的体重可降低这种风险。与围产期环境因素相比,遗传因素在决定婴儿 HBV 疫苗接种反应方面起主导作用(91%)。