The tip of the "celiac iceberg" in China: a systematic review and meta-analysis

Abstract

Objective: Until recently, celiac disease was considered to be rare in China. We aimed to estimate its true status.

Methods: By searching the MEDLINE database and four Chinese full-text databases (CNKI, CBM, VIP and WANFANG) (up to August 2012), as well as two HLA allele frequency net databases and the Chinese Statistics Yearbook databases, we systematically reviewed the literature on definite and suspected cases of celiac disease, the predisposing HLA allele frequencies, and on gluten exposure in China. Meta-analysis was performed by analyzing DQ2, DQ8 and DQB1*0201 gene frequencies and heterogeneity in populations from different geographic regions and ethnicities in China.

Results: At present, the number of reported celiac disease cases is extremely low in China. The frequencies of the HLA-DQ2.5 and HLA-DQ8 haplotypes were 3.4% (95% confidence interval 1.3-5.5%) and 2.1% (0.1-4.1%), respectively. HLA-DQ2 and HLA-DQ8 antigen frequencies were 18.4% (15.0-21.7%) and 8.0% (4.5-11.4%), respectively. The frequency of the DQB1*0201 allele was 10.5% (9.3-11.6%) and it was more common in the northern Chinese than in the southern Chinese populations. The chance of being exposed to gluten is rapidly increasing all over China nowadays.

Conclusion: The data on HLA haplotyping, in conjunction with increasing wheat consumption, strongly suggests that the occurrence of celiac disease is more common in China than currently reported. Coordinated measures by the Chinese government, medical and agricultural research institutions, and food industries, would be justified to create more awareness about celiac disease and to prevent it becoming a medical and societal burden.

Figure 1. Flow diagram for search results.

A: Flow chart for search results of celiac disease cases in the Chinese population. B: Flow chart for search results of CD-predisposing gene frequencies in the Chinese population. n, number of records; *In cases with both DQB1*0201 and DQB1*0201/02 allele frequencies of individuals from the same province, only the data of the DQB1*0201 allele were included in this research; ^#Four records included data on haplotypes and DQB1*0201 or DQB1*0201/02.

Figure 2. The frequencies and weightings of HLA-DQ2.5 and HLA-DQ8 haplotypes in the Chinese population.

A: HLA-DQ2.5; B: HLA-DQ8. Abbreviations: CI, confidence interval. The data sources are given in Table S1.

Figure 3. The frequencies and weightings of HLA- DQ2 and HLA-DQ8 antigens in the Chinese population.

A: HLA-DQ2; B: HLA-DQ8. Antigen frequency  =  sum of each individual antigen/n, where n  =  total number of subjects. Abbreviations: CI, confidence interval. The data sources are given in Table S2.

Figure 4. The DQB1*0201 allele frequency and its weighting in Chinese populations.

Abbreviations: CI, confidence interval. The data sources are given in Table S3.

Figure 5. The frequency of DQB1*0201 or DQB1*0201/02 in Chinese populations.

A: The DQB1*0201 or DQB1*0201/02 allele frequency in Chinese populations originated from inhabitants of 21 regions. The data from Jiangsu give the frequency of DQB1*0201/02, and the data from the other 20 regions are the frequency of DQB1*0201; B: The DQB1*0201 or DQB1*0201/02 allele frequencies of 21 ethnic minorities originated from nine geographic regions, and for the Han from 14 specific regions. The data for the Ewenki (Inner Mongolia), Dong (Guizhou), Miao (Guizhou), Jing (Guangxi), Naxi (Yunnan), Bai (Yunnan), Yao (Yunnan), and Han (Jiangsu) are the frequencies for DQB1*0201/02, and the others are the frequencies for DQB1*0201. The data sources are given in Table S3 and Table S4.

Figure 6. The per capita annual consumption of wheat and rice in rural households and urban households in 2009.

In rural areas, the rice and wheat consumption are calculated on a dry, rough (unprocessed, unhusked or unmilled) weight basis. In urban households, the rice and wheat flour consumption are calculated on a processed (husked or milled) weight basis. Data sources (2010): China Yearbook of Rural Household Survey; Gansu Development Yearbook; Xinjiang Production & Construction Group Statistical Yearbook; Statistics yearbooks from different provinces (Inner Mongolia, Liaoning, Jilin, Henan, Shaanxi, Jiangsu, Zhejiang, Guangdong).