Concordance, disease progression, and heritability of coeliac disease in Italian twins
Concordance, disease progression, and heritability of coeliac disease in Italian twins
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DOI：
10.1136/gut.2005.083964
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发表时间：
2006-06-01
期刊：
影响因子：
24.5
通讯作者：
Stazi, MA
中科院分区：
文献类型：
--
作者：
Nisticò, L;Fagnani, C;Stazi, MA
背景和目的：我们采用双胞胎方法来解开腹腔疾病（CD）易感性的遗传和环境因素。我们估计疾病的一致率的接合性和HLA基因型，不一致的时间，疾病的进展率，和heritability.Methods：我们交联的意大利双胞胎登记处与意大利腹腔疾病协会的会员名单，并招募了23个单卵（MZ）和50个双卵（DZ）双胞胎对至少有一个受影响的成员。通过DNA指纹图确定合子型，并对HLA-DQ和DR等位基因进行基因分型。通过抗肌内膜抗体、抗人组织转谷氨酰胺酶抗体和肠活检来确定疾病状态。结果：MZ（先证者83.3%，成对71.4%）的一致性显着高于DZ（先证者16.7%，成对9.1%）对。一致性不受双胞胎性别或HLA基因型的影响，MZ与CD的发生显著相关（考克斯校正风险比14.3（95%置信区间4.0-50.3））。在90%的一致配对中，不一致时间为（2年）。MZ和DZ双胞胎在5年内分别有70%和9%的累积概率患有有症状或无症状形式的CD。ACE（加性遗传，共同和非共享的环境因素）模型下，与CD人口患病率为1/91和1/1000，遗传力估计分别为87%和57%.Conclusion：MZ对有很高的概率是一致的，无论性别或HLA基因型。大多数受影响的双胞胎在两年内得到诊断。表型变异的一个显着比例是由于遗传因素。
Background and aims: 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.Methods: 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.Results: 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 (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.Conclusion: 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.