The Phenotype of Celiac Disease Has Low Concordance between Siblings, Despite a Similar Distribution of HLA Haplotypes

Nutrients

Katri Kaukinen¹  Teea Salmi¹  Henna Pekki¹  Katri Lindfors¹  Saana Kauma¹  Heini Huhtala²  Päivi Saavalainen³  Kalle Kurppa⁴  Laura Kivelä⁴ 

[1] Celiac Disease Research Centre, Faculty of Medicine and Life Sciences, Tampere University, 33520 Tampere, Finland;Faculty of Social Sciences, Tampere University, 33520 Tampere, Finland;Research Program Unit, Immunobiology, and Department of Medical and Clinical Genetics, University of Helsinki, 00014 Helsinki, Finland;Tampere Centre for Child Health Research, Tampere University and Tampere University Hospital, 33521 Tampere, Finland;

关键词: celiac disease;    sibling;    phenotype;    gluten-free diet;    environmental factors;    genotype;   

DOI  :  10.3390/nu11020479

来源: DOAJ

【 摘 要 】

The factors determining the presentation of celiac disease are unclear. We investigated the phenotypic concordance and the distribution of human leukocyte antigen (HLA) risk haplotypes in affected siblings. One hundred sibling pairs were included. Clinical and histological parameters and HLA haplotypes were compared between the first diagnosed indexes and their siblings. The phenotype was categorized into gastrointestinal, extra-intestinal, malabsorption/anemia, and asymptomatic. The phenotype was fully concordant in 21 pairs. The most common concordant phenotype was gastrointestinal (14 pairs). Indexes had more anemia/malabsorption and extra-intestinal symptoms than siblings (45% vs. 20%, p < 0.001 and 33% vs. 12%, p < 0.001, respectively). Twenty siblings and none of the indexes were asymptomatic. The indexes were more often women (81% vs. 63%, p = 0.008). They were also more often seronegative (11% vs. 0%, p = 0.03) and younger (37 vs. 43 year, p < 0.001), and had more severe histopathology (total/subtotal atrophy 79% vs. 58%, p = 0.047) at diagnosis. The indexes and siblings were comparable in other disease features. Pairs with discordant presentation had similar HLA haplotypes more often than the concordant pairs. The phenotype was observed to vary markedly between siblings, with the indexes generally having a more severe presentation. HLA did not explain the differences, suggesting that non-HLA genes and environmental factors play significant roles.

【 授权许可】

Unknown