高胆固醇血症与 12q24 基因座内的候选基因。

Hypercholesterolemia and a candidate gene within the 12q24 locus.

机构信息

Laboratory of Molecular Genetics of Complex and Monogenic Disorders, Department of Medicine and Cellular & Molecular Physiology and Biostatistics, Penn State University and M.S. Hershey Medical Center, Hershey, PA, USA.

出版信息

Cardiovasc Diabetol. 2011 May 9;10:38. doi: 10.1186/1475-2840-10-38.

DOI:10.1186/1475-2840-10-38

PMID:21554682

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3116465/

Abstract

BACKGROUND

The 12q24 locus entails at least one gene responsible for hypercholesterolemia. Within the 12q24 locus lies the gene of proteasome modulator 9 (PSMD9). PSMD9 is in linkage with type 2 diabetes (T2D), T2D-nephropathy and macrovascular pathology in Italian families and PSMD9 rare mutations contribute to T2D.

AIMS

In the present study, we aimed at determining whether the PSMD9 T2D risk single nucleotide polymorphisms (SNPs) IVS3 + nt460 A > G, IVS3 + nt437 T > C and E197G A > G are linked to hypercholesterolemia in 200 T2D Italian families.

METHODS

We characterized 200 Italian families for presence and/or absence of hypercholesterolemia characterized by LDL levels ≥ 100 mg/dl in drug-naïve patients and/or presence of a diagnosis of hypercholesterolemia in a patient treated with statin medication. The phenotypes were described as unknown in all cases in which the diagnosis was either unclear or the data were missing. We tested in the 200 Italians families for evidence of linkage of the PSMD9 SNPs with hypercholesterolemia. The non-parametric linkage analysis was performed for the qualitative phenotype by using the Merlin software; the Lod score and correspondent P-value were calculated. For the significant linkage score, 1000 replicates were performed to calculate the empirical P-value.

RESULTS

The PSMD9 gene SNPs studied show linkage to hypercholesterolemia. The results are not due to random chance.

CONCLUSIONS

PSMD9 should be tested in all populations reporting linkage to hypercholesterolemia within the chromosome 12q24 locus. The impact of this gene on hypercholesterolemia and contribution to cardio- and cerebrovascular events may be high.

摘要

背景

12q24 基因座至少包含一个导致高胆固醇血症的基因。在 12q24 基因座内，存在蛋白酶体调节剂 9（PSMD9）基因。PSMD9 与意大利家族的 2 型糖尿病（T2D）、T2D-肾病和大血管病变相关联，并且 PSMD9 罕见突变会导致 T2D。

目的

在本研究中，我们旨在确定 PSMD9 T2D 风险单核苷酸多态性（SNP）IVS3 + nt460 A > G、IVS3 + nt437 T > C 和 E197G A > G 是否与 200 个意大利 T2D 家族的高胆固醇血症相关。

方法

我们对 200 个意大利家族进行了特征描述，以确定是否存在或不存在 LDL 水平≥100mg/dl 的药物初治患者的高胆固醇血症特征，或接受他汀类药物治疗的患者存在高胆固醇血症的诊断。在所有诊断不明确或数据缺失的情况下，表型均描述为未知。我们在 200 名意大利人家庭中测试了 PSMD9 SNP 与高胆固醇血症之间的连锁证据。使用 Merlin 软件对定性表型进行非参数连锁分析；计算 Lod 得分和相应的 P 值。对于显著的连锁得分，进行了 1000 次重复以计算经验 P 值。