HLA-DQ genotype distribution and risk evaluation of celiac disease in Northwest China

Abstract

Background

Celiac disease (CD) is an autoimmune small bowel disease. Genetic susceptibility for CD is mainly determined by the human leukocyte antigen (HLA)-DQ haplotypes. The risk of CD conferred by HLA genotypes varies geographically and across populations, however, this has not yet been documented in Chinese patients with CD.

Aims

To investigate the distribution of HLA-DQ and the related risks of CD development in Northwest China.

Methods

A total of 75 CD patients and 300 healthy individuals were genotyped for HLA-DQ using the Illumina NextSeq, and the relative risks of the different genotypes were evaluated.

Results

In total, 68.00% of CD patients and 21.00% of controls carried HLA-DQ2.5 heterodimers (p < 0.001). We identified four CD risk gradients. Individuals carrying a double dose of DQB1*02 had the highest risk of developing CD (1:16); however, with heterozygosis (DQB1*02:02/DQB1*02:01) having the highest risk (1:9). HLA-DQ2.5 individuals with a single copy of HLA-DQB1*02, in either the cis or trans configuration, were at a medium risk (1:38). Non-DQ2.5 carriers of DQ8 or DQ2.2 were at low risk, while only carriers of DQ7.5 or DQX.5 were at very low risk. Patients with the HLA-DQ2.5 genotype had more severe mucosal damage compared with the HLA-DQ2.5 genotype negative CD patients (70.59% vs. 41.67%, p = 0.016).

Conclusion

Genetic susceptibility to CD is highly prevalent in the Northwest Chinese population and the highest risk of developing CD was associated with the DQ2.5/DQ2.2 genotype. The DQ2.5 allele is involved in the severity of mucosal injury.

Keywords:

• Celiac disease
• HLA typing
• genetic risk

Acknowledgments

We thank all medical staff and technicians who helped and agreed to participate in this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Supported by Hospital Project of People’s Hospital of Xinjiang Uygur Autonomous Region [NO. 20200406].