Leak Tennille S, Keene Keith L, Langefeld Carl D, Gallagher Carla J, Mychaleckyj Josyf C, Freedman Barry I, Bowden Donald W, Rich Stephen S, Sale Michèle M
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Mol Genet Metab. 2007 Sep-Oct;92(1-2):145-50. doi: 10.1016/j.ymgme.2007.05.014. Epub 2007 Jul 6.
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 282 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 Pa=0.00014), rs1609659 (Pa=0.028), rs4814597 (Pa=0.039) and rs2269023 (Pa=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.
在一项针对非裔美国人（AA）家庭的2型糖尿病（T2DM）全基因组扫描中，有序子集分析（OSA）为诊断年龄较晚的一个子集中20号染色体短臂的连锁提供了证据（最大对数优势比2.57，P = 0.008）。前蛋白转化酶枯草杆菌蛋白酶/kexin 2型（PCSK2）基因位于该连锁峰的对数优势比-1区间内。在380名患有T2DM和终末期肾病（T2DM-ESRD）的无亲缘关系的AA个体、278名AA对照、96名欧洲裔美国人（EA）和120名约鲁巴尼日利亚人（YRI）对照中，对该基因的29个单核苷酸多态性（SNP）进行了基因分型。此外，在所有AA受试者、120名YRI和282名EA对照中对22个祖先信息标记（AIM）进行了基因分型。ADMIXMAP用于模拟混合分布并生成等位基因和单倍型关联的得分检验。在4个SNP中观察到与T2DM的关联：rs2021785（混合调整后Pa = 0.00014）、rs1609659（Pa = 0.028）、rs4814597（Pa = 0.039）和rs2269023（Pa = 0.043）。没有一个PCSK2 SNP与T2DM诊断时的年龄相关。PCKS2基因中的一个变体rs2021785似乎在这个AA人群对T2DM的易感性中起作用。
