根據(jù)一項人類基因組研究,，一個人出現(xiàn)年齡相關(guān)性黃斑性變（AMD）的風險可能與幫助調(diào)節(jié)HDL膽固醇水平的一個基因有關(guān),。
Johanna Seddon及其同事搜索了將近1000位晚期AMD患者并發(fā)現(xiàn)了與該病有關(guān)的幾個候選基因，最明顯的是LIPC基因的一個變種,。LIPC攜帶著負責合成一種催化HDL（也就是所謂的“好膽固醇”）代謝的酶的遺傳編碼。
此前的研究表明HDL信號傳導路徑和AMD有關(guān),，當前的這些發(fā)現(xiàn)表明了AMD風險的增加或減少與膽固醇水平不穩(wěn)定的關(guān)聯(lián),。這組作者提出，HDL和AMD之間的遺傳關(guān)聯(lián)并非一個直接的因果關(guān)系,，而可能代表了一個多效的關(guān)系,，即單個基因可以決定看上去不相關(guān)的性狀。
在一篇相關(guān)論文中,，Anand Swaroop及其同事也報告了LIPC和同樣的HDL路徑的關(guān)聯(lián),，他們提出進一步研究HDL信號傳導可能提供關(guān)于AMD治療和預防的見解。(生物谷Bioon.com)
延伸閱讀：
nature最新報道：以色列培育出無膽固醇基因鼠
Cell Metabolism：確認20種調(diào)節(jié)膽固醇的基因
生物谷推薦原文出處：
PNAS doi:10.1073/pnas.0912019107
Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC)
Benjamin M. Nealea,b,c,1, Jesen Fagernessa,b,1, Robyn Reynoldsd, Lucia Sobrine, Margaret Parkerd, Soumya Raychaudhuria,b, Perciliz L. Tanf, Edwin C. Ohf, Joanna E. Merriamg, Eric Souiedh, Paul S. Bernsteini, Binxing Lii, Jeanne M. Fredericki, Kang Zhangi,j, Milam A. Brantley Jr.k,l, Aaron Y. Leek, Donald J. Zackf, Betsy Campochiarof, Peter Campochiarof, Stephan Ripkea,b, R. Theodore Smithg, Gaetano R. Barileg, Nicholas Katsanism, Rando Allikmetsg,n, Mark J. Dalya,b,2, and Johanna M. Seddond,o,1,2
Advanced age-related macular degeneration (AMD) is the leading cause of late onset blindness. We present results of a genome-wide association study of 979 advanced AMD cases and 1,709 controls using the Affymetrix 6.0 platform with replication in seven additional cohorts (totaling 5,789 unrelated cases and 4,234 unrelated controls). We also present a comprehensive analysis of copy-number variations and polymorphisms for AMD. Our discovery data implicated the association between AMD and a variant in the hepatic lipase gene (LIPC) in the high-density lipoprotein cholesterol (HDL) pathway (discovery P = 4.53e-05 for rs493258). Our LIPC association was strongest for a functional promoter variant, rs10468017, (P = 1.34e-08), that influences LIPC expression and serum HDL levels with a protective effect of the minor T allele (HDL increasing) for advanced wet and dry AMD. The association we found with LIPC was corroborated by the Michigan/Penn/Mayo genome-wide association study; the locus near the tissue inhibitor of metalloproteinase 3 was corroborated by our replication cohort for rs9621532 with P = 3.71e-09. We observed weaker associations with other HDL loci (ABCA1, P = 9.73e-04; cholesterylester transfer protein, P = 1.41e-03; FADS1-3, P = 2.69e-02). Based on a lack of consistent association between HDL increasing alleles and AMD risk, the LIPC association may not be the result of an effect on HDL levels, but it could represent a pleiotropic effect of the same functional component. Results implicate different biologic pathways than previously reported and provide new avenues for prevention and treatment of AMD.
