Association of the proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene with type 2 diabetes in an African American population

Abstract

In a genome-wide scan for type 2 diabetes (T2DM) in African American (AA) families, ordered subsets analysis (OSA) provided evidence for linkage to chromosome 20p in a subset with later age at diagnosis (max. LOD 2.57, P = 0.008). The proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene is within the LOD-1 interval of this linkage peak. Twenty-nine single nucleotide polymorphisms (SNPs) were genotyped across this gene in 380 unrelated AA individuals with T2DM and end-stage renal disease (T2DM-ESRD), 278 AA controls, 96 European Americans (EA) and 120 Yoruba Nigerian (YRI) controls. In addition, 22 ancestry-informative markers (AIMs) were genotyped in all AA subjects, 120 YRI, and 96 EA controls. ADMIXMAP was used to model the distributions of admixture and generate score tests of allelic and haplotypic association. Association with T2DM was observed among 4 SNPs: rs2021785 (admixture-adjusted P a = 0.00014), rs1609659 (P a = 0.028), rs4814597 (P a = 0.039) and rs2269023 (P a = 0.043). None of the PCSK2 SNPs were associated with age at T2DM diagnosis. A variant in the PCKS2 gene, rs2021785, appears to play a role in susceptibility to T2DM in this AA population.

Effect of a common variant of the PCSK2 gene on reduced insulin secretion

“…Variants in the PCSK2 gene have previously been associated with type 2 diabetes in African [9], Japanese [10] and Chinese [11] individuals, but not, to our knowledge, European populations. Here we report an independent signal in intron 2 of PCSK2 in Scandinavian populations that was not correlated with previously reported variants in African (rs2021785), Japanese (microsatellite marker in intron 2) and Chinese (rs2021785) populations.…”

“…PCSK2 is expressed in the brain and the pancreatic islets. Variants of the PCSK1 and PCSK2 genes have previously been linked to type 2 diabetes and obesity [7][8][9][10][11]. The aims of the current study were to study the association between genetic variants of the PCSK2 gene and insulin secretion, and to explore the effect on risk of type 2 diabetes.…”

Genetic Variation and Adaptation in Africa: Implications for Human Evolution and Disease

“…Additionally, the level of African or European ancestry in African Americans not only varies by individual but also by genomic region (Bryc et al 2009). To identify genetic factors mediating disease predisposition in populations of recent African descent, like African Americans, a number of different approaches have been employed (Dong et al 1999;Smith et al 2004;Malhotra et al 2005;Leak et al 2007;Adeyemo et al 2009;Sale et al 2009;McDonough et al 2011). One of these, called admixture mapping, is based on the premise that if a trait or disease of interest has a different prevalence in the parental populations prior to admixture, then it is likely that the genetic variation causing the disease or trait of interest in the admixed population is associated with chromosomal segment(s) derived from that parental population where the disease or trait is more prevalent .…”

视网膜神经节细胞-5应激损伤后原蛋白转化酶-2和羧基肽酶-E介导的神经肽加工

“…They are expressed together or separately in functional cells in both vertebrates and invertebrates. The mammalian PCs have been demonstrated to involve in several diseases, such as HIV, hepatitis B, severe acute respiratory syndrome (SARS), anthrax, cancer, Alzheimer's disease, arthritis, stroke, glaucoma, and diabetes [5][6][7][8][9][10] .…”