Association of SERPINE1 rs6092 with type 2 diabetes and related metabolic traits in a Chinese population.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-I), encoded by SERPINE1 gene, is a member of the serine protease inhibitor superfamily, and polymorphisms in SERPINE1 have been reported to be associated with type 2 diabetes (T2D). This study investigated whether the polymorphism in PAI-I contribute to the risk for T2D.

METHODS: A 1:1 case-control study was conducted to investigate the association of rs6092 in SERPINE1 with T2D and diabetes-related metabolic traits, including body mass index, waist circumference (WC), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol, low density lipoprotein cholesterol, fasting plasma glucose and glycosylated hemoglobin (HbA1c) in a Chinese population, with a total of 1572 subjects (786 T2D patients and 786 healthy controls). The polymorphism was genotyped based on MassARRAY genotyping system.

RESULTS: The AA genotype and A allele of rs6092 exerted a protective effect on T2D risk (odds ratio (OR) = 0.431 and 0.630, respectively). In a recessive model, we also observed the protective association of rs6092 with T2D (OR = 0.195). The above associations were only observed in men. In female patients, there was a significant difference in HbA1c level between the AA homozygotes and GG homozygotes, as well as between the AA homozygotes and combined GG and GA genotypes. In male patients, the WC level in the subjects carrying AA genotype was lower than those in the subjects with GG genotype (P = 0.000), and the association was also significant in a recessive model (P = 0.000). Additionally, there was a significant difference in TG level between the AA homozygotes and GG homozygotes (P = 0.017), as well as the AA homozygotes and combined GG and GA genotypes (P = 0.032).

CONCLUSIONS: Our study suggests that the A allele and AA genotype of rs6092 may protect against T2D, and have a protective effect on WC, but a negative effect on TG in men, while may contribute to a lower HbA1c level in women.