Two-stage association study to identify the genetic susceptibility of a novel common variant of rs2075290 in ZPR1 to type 2 diabetes

Abstract

The SNP of rs964184 in ZPR1 has recently been associated with type 2 diabetes mellitus (T2DM) in Japanese individuals. To comprehensively investigate the association of common variants in ZPR1 with T2DM in Han Chinese individuals, we designed a two-stage case-control study of 3,505 T2DM patients and 6,911 unrelated healthy Han Chinese individuals. A total of 24 single nucleotide polymorphisms (SNPs) were genotyped, and single-SNP association, imputation and gender-specific association analyses were performed. To increase the coverage of genetic markers, we implemented imputation techniques to extend the number of tested makers to 280. A novel SNP, rs2075290, and the previously reported SNP, rs964184, were significantly associated with T2DM in the two independent datasets, and individuals harboring the CC genotype of rs2075290 and GG genotype of rs964184 exhibited higher levels of fasting plasma glucose (FPG) and blood hemoglobin A1c (HbA1c) than individuals of other genotypes. Additionally, haplotype analyses indicated that two haplotype blocks containing rs2075290 or rs964184 were also significantly associated with T2DM. In summary, these results suggest that ZPR1 plays an important role in the etiology of T2DM, and this gene might be involved in abnormal glucose metabolism.

Genome wide analysis of gene expression changes in skin from patients with type 2 diabetes

“…The ZPR1 binds to the promoter of peroxisome proliferator-activated receptor gamma (PPARG) proteins 1 and 2, which play a key role in insulin sensitivity and obesity [86,87]. A previous study reported the evidence linking the genetic susceptibility of common variants in ZPR1 to type 2 diabetes with the levels of fasting plasma glucose and blood hemoglobin A1c, suggesting ZPR1 might be involved in abnormal glucose metabolism [88]. However, the expression tendency seems to be different in skin tissue and others.…”

Evaluation of the Relationship Between Common Variants in the TLR-9 Gene and Hip Osteoarthritis Susceptibility

“…With the rapid development of high-throughput sequencing, although more and more susceptibility variants of complex diseases have been identified (Guan et al, 2013(Guan et al, , 2014(Guan et al, , 2016a(Guan et al, , 2016b(Guan et al, , 2016cLiu et al, 2014;Zhang et al, 2018a). In recent years, researchers have identified strong association signals between the TLR-9 gene and the risk of KOA in both Han Chinese and Turkish populations (Su et al, 2012a;Balbaloglu et al, 2017;Zheng et al, 2017).…”

Relationship of common variants in Interleukin 33 gene with susceptibility and prognosis of osteosarcoma in Han Chinese population

“…Nevertheless, we have applied some criteria to restrict the genetic background of our study subjects to minimize their genetic heterogeneity. Thus, due to the subject individuals from the same geographical area, although the potential population stratification cannot be completely excluded, our sampling strategy can effectively avoid significant population stratification to the greatest extent [37][38][39][40][41][42] . Another limitation is that this study is not a randomized clinical trial, thus selection bias might be present.…”