Exploration of shared genetic susceptibility loci between type 1 diabetes and rheumatoid arthritis in the Pakistani population

Muhammad Muaaz Aslam,Eleanor Feingold,Kang-Hsien Fan,Attya Bhatti,Sidrah Jahangir,F Yesim Demirci,M Ilyas Kamboh,Peter John

doi:10.1186/s13104-019-4590-8

Muhammad Muaaz Aslam, Eleanor Feingold + Show 6 more

Open Access

https://doi.org/10.1186/s13104-019-4590-8

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Abstract

ObjectiveType 1 diabetes (T1D) and rheumatoid arthritis (RA) are autoimmune diseases. It is known that certain genetic loci and factors that increase the overall autoimmunity risk can be shared among different autoimmune diseases. We sought to replicate seven T1D-related SNPs (single nucleotide polymorphisms) that have been previously reported to be associated with RA susceptibility in a small set of mixed family-based and case–control Pakistani sample in a relatively large and independent RA case–control sample from the same population. Seven T1D-associated SNPs (GLIS3/rs7020673, BACH2/rs11755527, SKAP2/rs7804356, GDSMB/rs2290400, C6orf173/rs9388489, LOC399716/rs947474 and DLK1-MEG2/rs941576) were genotyped in a large Pakistani RA case–control sample (n = 1959) using TaqMan® SNP genotyping assays.ResultsNone of the tested SNPs showed statistically significant association with RA susceptibility; however, one SNP (GLIS3/rs7020673) showed a trend for association (OR = 0.88, p = 7.99E−02). Our study has failed to replicate the previously reported association of seven T1D-associated SNPs with RA risk in a large sample from the same population. Thus, our results do not support a major role of these T1D SNPs in affecting RA susceptibility in the Pakistani population.

Highlights

Prevalence of autoimmune diseases is 3–5% in the general population [1, 2]
Our results do not support a major role of these Type 1 diabetes (T1D) single nucleotide polymorphisms (SNPs) in affecting rheumatoid arthritis (RA) susceptibility in the Pakistani population
Rheumatoid arthritis (RA) is a complex, systemic, chronic, inflammatory, autoimmune disease characterized by synovial inflammation of mainly small joints and autoantibodies production, which may lead to physical disability associated with the socioeconomic burden and in severe cases, an early death [8, 9]

Summary

Results

A total of 1959 unrelated RA case–control subjects were genotyped to replicate the previously reported association (by Kiani et al [23]) of seven T1D-associated SNPs with RA. All tested SNPs showed similar frequencies in our study as reported by Kiani et al [23]. Of the seven tested SNPs, only one (rs947474) was an upstream gene variant and the rest were intronic. None of the tested T1D-associated SNPs showed significant association with RA in our large replication sample. A trend for association (OR = 0.88; p = 7.99E−02, FDR = 2.93E−01) was observed for one intronic SNP (rs7020673) located in the GLIS3 gene (Table 1). Alleles (minor/ Variant type Previously reported results (Kiani et al Our replication results major). This study with MAFs ranging between 0.16 and 0.43, we had > 80% power to detect significant association at an effect size of ≥ 1.3 under the additive model

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