Epidemiology, genetics, clinical characteristics, and dietary risk factors of familial celiac disease in China: A cross-sectional study

Abstract

BACKGROUND

Celiac disease (CeD) is a gluten-induced autoimmune disorder of the intestine characterized by strong familial clustering. Compared with the general population, family members of CeD patients have a significantly increased risk of developing CeD. However, to our knowledge, no studies have investigated CeD families within the Chinese population; therefore, their epidemiological, genetic, clinical, and dietary characteristics remain largely unknown.

AIM

To investigate the epidemiological, HLA-DQ genotypic, clinical, and dietary characteristics of CeD in Chinese familial clusters.

METHODS

A cross-sectional survey was conducted, enrolling a total of 179 participants from 29 CeD families. CeD was confirmed using serum tissue transglutaminase screening combined with duodenal histopathological diagnosis. HLA-DQ genotyping was performed to obtain HLA-DQ genotype information for each family member and to assess their genetic risk. Demographic characteristics, CeD-related gastrointestinal and extra-gastrointestinal symptoms, comorbidities, laboratory parameters, and dietary habits were collected to evaluate the role of environmental factors in CeD.

RESULTS

The overall prevalence of CeD in these families was 28.9% (48/166). The prevalence among first-degree relatives (FDRs) was 15.2% (16/105), with the highest risk observed among siblings (20%, 9/45), followed by parents (14.3%, 3/21) and offspring (10.3%, 4/39). The prevalence among second-degree relatives was 12.1% (4/33). The prevalence was significantly higher in females than in males (35.2% vs 17.2%, P = 0.015). Individuals carrying the HLA-DQ2.5/DQ2.5 and DQ2.5/DQ2.2 genotypes exhibited the highest risk of CeD, with prevalence rates of 60% and 55%, respectively. CeD-positive individuals were more likely to experience chronic diarrhea, fatigue, malnutrition, thyroid disorders, and hematological conditions. In the FDR analysis, consumption of high-salt preserved foods and sharing toothbrushes were associated with an increased risk of CeD (P < 0.05). Additionally, CeD patients had lower free thyroxine 4 levels and higher thyroid peroxidase antibody and alanine aminotransferase levels. Among individuals with comparable HLA-DQ2.5 risk, CeD-positive subjects exhibited more severe gastrointestinal and extra-intestinal symptoms. Furthermore, consumption of milk tea (made primarily from milk and brick tea) [adjusted odds ratio (aOR) = 2.785, 95% confidence interval (CI): 1.009-7.682] and of wheat (aOR = 3.104, 95%CI: 1.052-9.160) was associated with an increased risk of CeD (P < 0.05).

CONCLUSION

This study provides the first data on the prevalence and HLA-DQ genotyping profiles in Chinese CeD families and identifies multiple factors associated with the risk of CeD within these families. Screening for CeD among family members of patients with a confirmed CeD diagnosis is recommended. In particular, screening family members who carry high-risk HLA alleles and those with high gluten intake can facilitate early detection of CeD, thereby minimizing the adverse consequences of delayed diagnosis and improving patients’ quality of life.

Keywords: Celiac disease; China; Epidemiology; HLA-DQ2/8; Gastrointestinal symptoms; Dietary habits

Core Tip: This first systematic survey of 29 Chinese celiac disease (CeD) families revealed a prevalence of 15.2% among first-degree relatives and 12.1% among second-degree relatives. Carriers of HLA-DQ2.5/DQ2.2 and DQ2.5/DQ2.5 genotypes exhibited the highest risk. Among individuals with comparable genetic risk, higher wheat and milk tea consumption were associated with increased CeD risk, suggesting that dietary factors may modulate disease expression beyond genetic susceptibility.