第一项基于大规模人群的乳糜泻双胞胎研究。
The first large population based twin study of coeliac disease.
作者信息
Greco L, Romino R, Coto I, Di Cosmo N, Percopo S, Maglio M, Paparo F, Gasperi V, Limongelli M G, Cotichini R, D'Agate C, Tinto N, Sacchetti L, Tosi R, Stazi M A
机构信息
Department of Paediatrics, University of Naples Federico II, Naples, Italy.
出版信息
Gut. 2002 May;50(5):624-8. doi: 10.1136/gut.50.5.624.
BACKGROUND AND AIMS
The genetic load in coeliac disease has hitherto been inferred from case series or anecdotally referred twin pairs. We have evaluated the genetic component in coeliac disease by estimating the concordance rate for the disease among twin pairs in a large population based study.
METHODS
The Italian Twin Registry was matched with the membership lists of a patient support group. Forty seven twin pairs were recruited and screened for antiendomysial (EMA) and antihuman-tissue transglutaminase (anti-tTG) antibodies; zygosity was verified by DNA fingerprinting and twins were typed for HLA class II DRB1 and DQB1 molecules.
RESULTS
Concordance rates for coeliac disease differ significantly between monozygotic (MZ) (0.86 probandwise and 0.75 pairwise) and dizygotic (DZ) (0.20 probandwise and 0.11 pairwise) twins. This is the highest concordance so far reported for a multifactorial disease. A logistic regression model, adjusted for age, sex, number of shared HLA haplotypes, and zygosity, showed that genotypes DQA10501/DQB10201 and DQA10301/DQB10302 (encoding for heterodimers DQ2 and DQ8, respectively) conferred to the non-index twin a risk of contracting the disease of 3.3 and 1.4, respectively. The risk of being concordant for coeliac disease estimated for the non-index twin of MZ pairs was 17 (95% confidence interval 2.1-134), independent of the DQ at risk genotype.
CONCLUSION
This study provides substantial evidence for a very strong genetic component in coeliac disease, which is only partially due to the HLA region.
背景与目的
乳糜泻的遗传负荷迄今是从病例系列或偶尔提及的双胞胎对中推断出来的。我们通过在一项基于大人群的研究中估计双胞胎对中该疾病的一致率，评估了乳糜泻的遗传成分。
方法
将意大利双胞胎登记处与一个患者支持小组的成员名单进行匹配。招募了47对双胞胎，并对其进行抗肌内膜（EMA）和抗组织转谷氨酰胺酶（抗tTG）抗体筛查；通过DNA指纹图谱验证合子性，并对双胞胎进行HLA II类DRB1和DQB1分子分型。
结果
乳糜泻在同卵双胞胎（MZ）（先证者一致率为0.86，成对一致率为0.75）和异卵双胞胎（DZ）（先证者一致率为0.20，成对一致率为0.11）中的一致率有显著差异。这是迄今为止报道的多因素疾病中最高的一致率。一个经年龄、性别、共享HLA单倍型数量和合子性调整的逻辑回归模型显示，基因型DQA10501/DQB10201和DQA10301/DQB10302（分别编码异二聚体DQ2和DQ8）使非先证者双胞胎患该疾病的风险分别为3.3和1.4。MZ对中未患病的双胞胎患乳糜泻的一致风险估计为17（95%置信区间2.1 - 134），与有风险的DQ基因型无关。
结论
本研究为乳糜泻中非常强的遗传成分提供了大量证据，这仅部分归因于HLA区域。
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