Association of GTF2I gene polymorphisms with renal involvement of systemic lupus erythematosus in a Chinese population

Abstract

The purposes of the study was to validate the relationship between General transcription factor II-I (GTF2I) genetic variants and kidney involvements of systemic lupus erythematosus (SLE) patients in a Chinese Han population. Samples from 400 SLE patients and 400 age- and sex-matched healthy controls were collected and genotyped by improved multiplex ligation detection reaction technique. The relationship between gene polymorphism of rs117026326, rs73366469, and susceptibility, progression of SLE were analyzed. The present study provided evidence that rs117026326 and rs73366469 were both associated with SLE susceptibility (both C vs T: P < .001). The analysis of dominant, recessive disease model provided us with further validation ( P < .001). Both gene polymorphisms are associated with a triad of disease manifestations among SLE patients. Patients carrying genotype TT of rs117026326 had lower 24-hour urinary total protein (24 hours UTP, g/24 hours), 24-hour urinary protein level (g/L·24 hours), lower frequency of the proteinuria and lupus nephritis (LN). Patients carrying genotype TT at rs73366469 had higher 24-hour urinary protein level, higher frequency of the proteinuria, LN and positive anti-dsDNA than those with other genotypes. This study identified the involvement of GTF2I gene polymorphisms in development of SLE, particularly in renal involvement.

Association of GTF2I, NFKB1, and TYK2 Regional Polymorphisms With Systemic Sclerosis in a Chinese Han Population

“…Our previous GWAS showed that GTF2I was the most strongly associated gene in Chinese Han patients with primary Sjögren’s syndrome (pSS) ( 23 ). Several association studies of candidate genes have revealed that the GTF2I gene is an important genetic susceptibility factor in SLE and RA ( 7 , 24 ). Furthermore, SSc, pSS, SLE, and RA are all connective tissue diseases and share many clinical features, particularly in aspects of immune activation ( 25 ).…”

“…Our results indeed confirmed that GTF2I SNPs rs117026326 and rs73366469 were strongly associated with SSc in the Chinese Han population. Interestingly, rs73366469 is located within conserved enhancers and overlaps with transcription start sites (TSS) for GTF2I , thereby demonstrating the meaningful regulation of GTF2I ( 24 ). Additionally, rs117026326 and rs73366469 displayed consistent allele, genotype, genetic model, and clinical association results because of their medium linkage disequilibrium.…”

Meta-analysis of genome-wide association study identifies FBN2 as a novel locus associated with systemic lupus erythematosus in Thai population

“…1 b, Table 2 ) in Thai population, and the variants at the PROS1C1 , NOTCH4 , HCP5 , C6orf10 , TAP2 , TNFSF4 , RasGRP3 , TERT , TNPO3-IRF5 , CXCR5 , GPR19 , SLC15A4 , and ITGAM loci showed suggestive evidence of associations with SLE ( p value < 5E−05, Supplementary Table 1 ). These loci have been found in several ancestries, including Han Chinese, Korean, North American, European, African, and Hispanic populations [ 31 , 32 ].…”

Meta-analysis of genome-wide association study identifies FBN2 as a novel locus associated with Systemic Lupus Erythematosus in Thai population

“…Of these loci, the HLA-DQA1, HLA-DRB1, STAT4, FAM167A-BLK, and GTF2I loci have reached the genome-wide signi cant threshold (p-value < 5E-08; Figure 1B, Table 2) in Thai population, and the variants at the PROS1C1, NOTCH4, HCP5, C6orf10, TAP2, TNFSF4, RasGRP3, TERT, TNPO3-IRF5, CXCR5, GPR19, SLC15A4, and ITGAM loci showed suggestive evidence of associations with SLE (p-value < 5E-05, Supplementary Table 1). These loci have been found in several ancestries, including Han Chinese, Korean, North American, European, African, and Hispanic populations [30,31].…”