健康双生子外周血CD4+和CD8+ T细胞亚群相对计数遗传度研究

目的：分析围生期及生命早期环境因素与外周血CD4+、CD8+ T细胞相对计数的关系，估计CD4+和CD8+ T细胞亚群的遗传度。方法：采用双生子研究设计，经纳入与排除标准选取在新疆医科大学第一附属医院、乌鲁木齐市妇幼保健医院、新疆维吾尔自治区人民医院、中国人民解放军乌鲁木齐总医院和乌鲁木齐市第一人民医院出生的健康双生子。收集研究对象一般家庭状况、母亲孕期及分娩状况、出生时状况等信息，在双生子满1周岁时进行体检。体重和身高等体格发育指标依照“1995年中国九市7岁以下儿童体格发育调查研究”标准进行测量。测定外周血CD4+和CD8+ T细胞亚群相对计数，并通过微卫星DNA基因分型技术进行卵型鉴定。CD4+和CD8+ T细胞亚群的遗传度估计应用Mx软件进行分析。结果：研究期间共有172对双生子进入分析，其中82对为(47.7%)同卵双生子（MZ），90对为异卵双生子(DZ)。Apgar评分与MZ、DZ组CD4+ T细胞相对计数呈弱正相关(rMZ=0.16,rDZ=0.14,P<0.05)。最终选择AE模型得到1岁幼儿外周血CD4+和CD8+ T细胞的遗传度分别为61.8%(95%CI:38.3%~74.8%)与57.3%(95%CI:34.5%~70.2%)。结论：1岁幼儿外周血CD4+和CD8+ T细胞亚群遗传度高于成人水平，Apgar评分或与CD4+和CD8+ T细胞亚群相对计数相关。

Heritability of CD4+ and CD8+ T-lymphocyte subsets of peripheral blood in healthy twins

Objectives：To observe environmental determinants and the heritability of CD4+ and CD8+ T-lymphocyte subsets in 1 year-old healthy twins. Methods：Twins born at 5 compresive hospitals in Urumqi including the First Teaching Hospital of Xinjiang Medical University, Materal and Child Care Hospital of Urumqi City, People′s Hospital of Xinjiang Uygur Autonomous Region, the PLA Hospital of Xinjiang and the First People′s Hospital of Urumqi City were recruited based on the inclusion and exclusion criteria after obtaining inform consent. Demographic and general information, family history, paternal life styles, maternal gestational and birth information, as well as feeding and growth development information of infants were collected by interview and medical records. The growth and development examinations were performed by using national unified instruments and protocols. Venous whole blood samples (2 mL) were obtained from all subjects using EDTA-K3 tubes and CD4+ and CD8+ T cell counts were examined on the same day by flow cytometry. Zygosity was determined by DNA-based microsatellite markers. Conventional statistical analyses were performed using Stata 11.0 software for Windows. Structural equation model was used to estimate the relative contribution of genetic and environmental effects to the CD4+ and CD8+ T-lymphocyte subsets number using Mx program. Results：Totally 172 healthy pairs of twins were enrolled into the study, consisting of 82 monozygotic (MZ) (47.7%) and 90 dizygotic (DZ) pairs. There was a positive but weak correlation between CD4+ T cells counts and Apgar score in both MZ twins and DZ twins (rMZ=0.16, rDZ=0.14, P<0.05). After model fitting, AE model showed the best performance to the continuous phenotypes for both CD4+ and CD8+ T-lymphocyte counts, additive genetic effect (i.e. heritability) explained 61.8%(95%CI:38.3%~74.8%) and 57.3%(95%CI:34.5%~70.2%) of variations of CD4+ and CD8+ T-lymphocyte counts, respectively. Unique environmental effect explained 38.2%(95% CI: 20.4~52.8%) and 42.7%(95%CI: 26.2%~61.9%) of the variations, respectively. Conclusions：The heritability of CD4+ and CD8+ T-lymphocyte counts was 0.62 and 0.57 in 1-year old infants respectively. Perinatal and early life environmental factors, such as Apgar score may be associated with CD4+ and CD8+ T-lymphocyte counts.