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新墨西哥人群中NAFLD易感基因及其与2型糖尿病和肥胖症的关联

NAFLD Susceptibility Genes and their Association with Type 2 Diabetes and Obesity in a New Mexico Population.

作者信息

Garner Cara J, Conn Carole A, Cohen Deborah, Luo Li, Castillo Joseph J, Shah Vallabh O, Garver William S

机构信息

Department of Individual Family and Community Education, Nutrition and Dietetics Program, Albuquerque, New Mexico, USA.

Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.

出版信息

J Diabetes Obes. 2015;2(2). doi: 10.15436/2376-0494.15.024. Epub 2015 Jul 27.

Abstract

OBJECTIVE

Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) that increase the risk of developing non-alcoholic fatty liver disease (NAFLD). One purpose of this study was to determine the frequencies of NAFLD susceptibility SNPs in a non-Hispanic white and Hispanic population who attended a clinic in northeast Albuquerque, NM. Another goal was to determine associations with selected indicators in this New Mexican population.

METHODS

This cohort study involving 168 volunteer subjects in the NM population (88 non-Hispanic whites, 63 Hispanics, 4 Native Americans, 11 Asian Americans, 2 unreported ethnicity). Eight SNPs within 6 NAFLD susceptibility genes including PNPLA3 (rs738409), LYPLAL1 (rs12137855), APOC3 (rs2854116, rs2854117), GCKR (rs780094, rs741038), FABP2 (rs1799883), PEMT (rs7946) were analyzed by genotyping using the TaqMan genotyping assay (Applied Biosystems, Foster City, CA). Statistical analyses were carried out using statistical package SAS 9.3.

RESULTS

The NAFLD allele frequencies were similar in non-Hispanic whites and Hispanics except for PNPLA3 (rs738409), FABP2 (rs1799883), and PEMT (rs7946). Eight SNPs in 5 NAFLD susceptibility genes were significantly associated OR marginally associated with selected indicators for NAFLD, metabolic syndrome, overweight, obesity, insulin resistance, type 2 diabetes, hypertension, dyslipidemia. No SNPs were significantly associated with the same indicator in both the non-Hispanic white and Hispanic groups.

CONCLUSIONS

In this population of non-Hispanic whites and Hispanics, there were only heterozygotes for the APOC3 derived alle le whereas for all other genes tested, both heterozygotes and homozygotes were found. Associations of alleles with indicators of chronic disease were different in non-Hispanic whites compared to Hispanics.

摘要

目的

全基因组关联研究已确定了增加非酒精性脂肪性肝病(NAFLD)发病风险的单核苷酸多态性(SNP)。本研究的一个目的是确定在新墨西哥州阿尔伯克基东北部一家诊所就诊的非西班牙裔白人和西班牙裔人群中NAFLD易感SNP的频率。另一个目标是确定与该新墨西哥人群中选定指标的关联。

方法

这项队列研究涉及新墨西哥州人群中的168名志愿者受试者(88名非西班牙裔白人、63名西班牙裔、4名美洲原住民、11名亚裔美国人、2名未报告种族)。使用TaqMan基因分型检测法(应用生物系统公司,加利福尼亚州福斯特城)对6个NAFLD易感基因内的8个SNP进行基因分型分析,这些基因包括PNPLA3(rs738409)、LYPLAL1(rs12137855)、APOC3(rs2854116、rs2854117)、GCKR(rs780094、rs741038)、FABP2(rs1799883)、PEMT(rs7946)。使用统计软件包SAS 9.3进行统计分析。

结果

除PNPLA3(rs738409)、FABP2(rs1799883)和PEMT(rs7946)外,非西班牙裔白人和西班牙裔人群中NAFLD等位基因频率相似。5个NAFLD易感基因中的8个SNP与NAFLD、代谢综合征、超重、肥胖、胰岛素抵抗、2型糖尿病、高血压、血脂异常的选定指标显著相关或边缘相关。在非西班牙裔白人和西班牙裔组中,没有SNP与相同指标显著相关。

结论

在这个非西班牙裔白人和西班牙裔人群中,APOC3衍生等位基因仅存在杂合子,而对于所有其他检测基因,均发现了杂合子和纯合子。与西班牙裔相比,非西班牙裔白人中,等位基因与慢性病指标的关联有所不同。

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