Evaluation of the Host Genetic Effects of Tuberculosis-Associated Variants Among Patients With Type 1 and Type 2 Diabetes Mellitus

Abstract

Abstract Background Understanding the link between tuberculosis (TB) and diabetes is increasingly important as public health responds to the growing global burden of noncommunicable diseases. Genetic association studies have identified numerous host genetic variants linked to TB; however, potential host genetic mechanisms linking TB and diabetes remain unexplored. Methods We used genetic and phenotypic data from the UK Biobank to evaluate the association of 6 previously reported TB-related host genetic variants (genome-wide significant associations from published studies) with diabetes. The study included 409 692 adults of European ancestry including 2177 with type 1 diabetes mellitus (T1DM) and 13 976 with type 2 diabetes mellitus (T2DM), defined by ICD-10 diagnosis codes. Results Of the 6 TB-associated single nucleotide polymorphisms (SNPs), 2 were associated with T1DM and 3 with T2DM, after adjusting for age, sex, body mass index, smoking, alcohol use, and population structure. After correction for multiple testing, SNPs rs2894257 and rs3135359 (HLA-DRA-DQA1) were associated with T1DM (rs2894257: odds ratio [OR], 1.32; 95% confidence interval [CI], 1.21–1.45; rs3135359: OR, 1.72; 95% CI, 1.57–1.88) and T2DM (rs2894257: OR, 1.11; 95% CI, 1.08–1.15; rs3135359: OR, 1.06; 95% CI, 1.025–1.096). The associations with T2DM weakened for rs2894257 and rs3135359 after further exclusion of probable T1DM cases defined by International Statistical Classification of Diseases and Related Health Problems (ICD-10) codes. SNP rs4733781 on chromosome 8 (ASAP1 gene) was associated with T2DM after exclusion of T1DM cases. Conclusions Our findings suggest that common host genetic effects may play a role in the molecular mechanism linking TB and diabetes. Future large genetic studies of TB and diabetes should focus on developing countries with high burdens of infectious and chronic diseases.