Nisticò L, Fagnani C, Coto I, Percopo S, Cotichini R, Limongelli M G, Paparo F, D'Alfonso S, Giordano M, Sferlazzas C, Magazzù G, Momigliano-Richiardi P, Greco L, Stazi M A
Genetic Epidemiology Unit, CNESPS, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italia.
Gut. 2006 Jun;55(6):803-8. doi: 10.1136/gut.2005.083964. Epub 2005 Dec 14.
We adopted the twin method to disentangle the genetic and environmental components of susceptibility to coeliac disease (CD). We estimated disease concordance rate by zygosity and HLA genotypes, discordance times, progression rates to disease, and heritability.
We crosslinked the Italian Twin Registry with the membership lists of the Italian Coeliac Disease Association and recruited 23 monozygotic (MZ) and 50 dizygotic (DZ) twin pairs with at least one affected member. Zygosity was assigned by DNA fingerprinting, and HLA-DQ and DR alleles were genotyped. Disease status was ascertained by antiendomysial, anti-human tissue transglutaminase antibodies, and bowel biopsy.
Concordance was significantly higher in MZ (83.3% probandwise, 71.4% pairwise) than in DZ (16.7% probandwise, 9.1% pairwise) pairs. Concordance was not affected by sex or HLA genotype of the co-twin and being MZ was significantly associated with the occurrence of CD (Cox adjusted hazard ratio 14.3 (95% confidence interval 4.0-50.3)). In 90% of concordant pairs the discordance time was <or=2 years. MZ and DZ co-twins had 70% and 9% cumulative probability of having symptomatic or silent forms of CD, respectively, within five years. Under ACE (additive genetic, common, and unshared environmental factors) models, with CD population prevalences of 1/91 and 1/1000, heritability estimates were 87% and 57%, respectively.
MZ pairs have a high probability of being concordant, regardless of sex or HLA genotype. Most of the affected co-twins receive a diagnosis within two years. A remarkable proportion of phenotypic variance is due to genetic factors.
我们采用双生子研究方法来剖析乳糜泻（CD）易感性的遗传和环境因素。我们通过同卵性和HLA基因型、不一致时间、疾病进展率以及遗传度来估计疾病一致性率。
我们将意大利双生子登记处与意大利乳糜泻协会的成员名单进行交叉比对，招募了至少有一名患病成员的23对同卵（MZ）双生子和50对异卵（DZ）双生子。通过DNA指纹图谱确定同卵性，并对HLA - DQ和DR等位基因进行基因分型。通过抗肌内膜、抗人组织转谷氨酰胺酶抗体和肠道活检来确定疾病状态。
MZ双生子对的一致性（先证者法为83.3%，成对法为71.4%）显著高于DZ双生子对（先证者法为16.7%，成对法为9.1%）。一致性不受双胞胎中另一成员的性别或HLA基因型影响，且MZ双生子与CD的发生显著相关（Cox调整风险比为14.3（95%置信区间4.0 - 50.3））。在90%的一致双生子对中，不一致时间≤2年。MZ和DZ双胞胎在5年内出现有症状或无症状形式CD的累积概率分别为70%和9%。在ACE（加性遗传、共同和非共享环境因素）模型下，CD人群患病率分别为1/91和1/1000时，遗传度估计值分别为87%和57%。
无论性别或HLA基因型如何，MZ双生子对患CD的一致性概率都很高。大多数受影响的双胞胎在两年内得到诊断。相当一部分表型变异是由遗传因素引起的。
