Edelman Deborah, Kalia Harmit, Delio Maria, Alani Mustafa, Krishnamurthy Karthik, Abd Mortadha, Auton Adam, Wang Tao, Wolkoff Allan W, Morrow Bernice E
Department of Genetics Albert Einstein College of Medicine 1301 Morris Park Ave. Bronx New York 10461.
Division of Gastroenterology and Liver Diseases Montefiore Medical Center and Albert Einstein College of Medicine Bronx New York 10461.
Mol Genet Genomic Med. 2015 Aug 11;3(6):558-69. doi: 10.1002/mgg3.168. eCollection 2015 Nov.
We explored potential genetic risk factors implicated in nonalcoholic fatty liver disease (NAFLD) within a Caribbean-Hispanic population in New York City. A total of 316 individuals including 40 subjects with biopsy-proven NAFLD, 24 ethnically matched non-NAFLD controls, and a 252 ethnically mixed random sampling of Bronx County, New York were analyzed. Genotype analysis was performed to determine allelic frequencies of 74 known single-nucleotide polymorphisms (SNPs) associated with NAFLD risk based on previous genome-wide association study (GWAS) and candidate gene studies. Additionally, the entire coding region of PNPLA3, a gene showing the strongest association to NAFLD was subjected to Sanger sequencing. Results suggest that both rare and common DNA variations in PNPLA3 and SAMM50 may be correlated with NAFLD in this small population study, while common DNA variations in CHUK and ERLIN1, may have a protective interaction. Common SNPs in ENPP1 and ABCC2 have suggestive association with fatty liver, but with less compelling significance. In conclusion, Hispanic patients of Caribbean ancestry may have different interactions with NAFLD genetic modifiers; therefore, further investigation with a larger sample size, into this Caribbean-Hispanic population is warranted.
我们在纽约市的加勒比裔西班牙人群体中探究了非酒精性脂肪性肝病（NAFLD）潜在的遗传风险因素。总共分析了316名个体，其中包括40名经活检证实患有NAFLD的受试者、24名种族匹配的非NAFLD对照者，以及从纽约布朗克斯县进行的252名种族混合随机抽样者。基于先前的全基因组关联研究（GWAS）和候选基因研究，进行了基因型分析，以确定与NAFLD风险相关的74个已知单核苷酸多态性（SNP）的等位基因频率。此外，对与NAFLD关联最强的基因PNPLA3的整个编码区进行了桑格测序。结果表明，在这项小规模人群研究中，PNPLA3和SAMM50中罕见和常见的DNA变异可能与NAFLD相关，而CHUK和ERLIN1中的常见DNA变异可能具有保护作用。ENPP1和ABCC2中的常见SNP与脂肪肝存在提示性关联，但显著性较弱。总之，加勒比血统的西班牙裔患者与NAFLD遗传修饰因子可能存在不同的相互作用；因此，有必要对这个加勒比裔西班牙人群体进行更大样本量的进一步研究。
