Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration.
Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration.
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血清脂质生物标志物和肝脂肪酶基因与年龄相关的黄斑变性。
DOI：
10.1016/j.ophtha.2010.07.009
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发表时间：
2010-10
期刊：
影响因子：
13.7
通讯作者：
Seddon JM
中科院分区：
文献类型：
--
作者：
Reynolds R;Rosner B;Seddon JM
在我们的全基因组关联研究中，发现高密度脂蛋白 (HDL) 胆固醇途径中的遗传变异肝脂肪酶 (LIPC) 与晚期年龄相关性黄斑变性 (AMD) 相关。我们评估了 LIPC 是否与血脂相关，并确定该基因和血脂是否与 AMD 独立相关。病例对照研究。黄斑变性和年龄相关性眼病进展研究 (AREDS) 辅助研究共有 458 名参与者，其中包括 318 名患有地理萎缩 (n = 123) 或新生血管疾病 (n = 195) 的晚期 AMD 病例以及 140 名对照者。对参与者进行了与 AMD 相关的 8 种变异的基因分型：两种 CFH 变异、C2、CFB、C3、CFI、ARMS2/HTRA1 基因区域和 LIPC。在研究开始时采集空腹血标本，并测定总胆固醇、低密度脂蛋白（LDL）、HDL和甘油三酯的血清水平。 Logistic 回归用于评估血脂、LIPC 基因型和 AMD 之间的关联。使用逻辑回归和线性回归确定 LIPC 和血清脂质之间的关系。 LIPC 和血清脂质与 AMD 的关联。 LIPC 基因的次要 T 等位基因与 AMD 风险降低相关（比值比 (OR) = 0.4，95% 置信区间 (CI) (0.2 – 0.9) p（T 等位基因数量趋势）= 0.01，控制年龄和性别。在晚期病例中，HDL 平均水平较低 (p = 0.05)，LDL 平均水平 (p = 0.04) 较高与对照组相比，较高的总胆固醇和 LDL 与 AMD 风险增加相关，在控制环境和遗传协变量的模型中，LIPC 的 T 等位基因与较高水平的 HDL 相关。然而，LIPC 基因的 HDL 升高等位基因与 AMD 风险降低相关。 AMD 与 LIPC 之间关联的具体机制需要进一步研究。
A genetic variant in the high density lipoprotein (HDL) cholesterol pathway, hepatic lipase (LIPC), was discovered to be associated with advanced age-related macular degeneration (AMD) in our genome-wide association study. We evaluated whether LIPC is associated with serum lipids and determined if the gene and serum lipids are independently associated with AMD. Case – control study. A total of 458 participants from the Progression Study of Macular Degeneration and the Age Related Eye Disease (AREDS) Ancillary study, including 318 advanced AMD cases with either geographic atrophy (n = 123) or neovascular disease (n = 195) and 140 controls. Participants were genotyped for 8 variants associated with AMD: two CFH variants, C2, CFB, C3, CFI, the ARMS2/HTRA1 gene region, and LIPC. Fasting blood specimens were obtained at study onset, and serum levels of total cholesterol, low density lipoprotein (LDL), HDL, and triglycerides were determined. Logistic regression was used to evaluate associations between serum lipids, LIPC genotype and AMD. The relationship between LIPC and serum lipids was determined using logistic and linear regression. LIPC and serum lipid associations with AMD. The minor T allele of the LIPC gene was associated with a reduced risk of AMD (Odds Ratio (OR) = 0.4, 95% Confidence Interval (CI) (0.2 – 0.9) p (trend for number of T alleles) = 0.01, controlling for age and sex. Mean level of HDL was lower (p =0.05), and mean level of LDL (p=0.04) was higher in cases of advanced AMD compared with controls. Higher total cholesterol and LDL were associated with increased risk of AMD with a p (trend) of 0.01 for both, in models controlling for environmental and genetic covariates. The T allele of LIPC was associated with higher levels of HDL. However, LIPC is associated with advanced AMD independent of HDL level. The HDL raising allele of the LIPC gene was associated with reduced risk of AMD. Higher total cholesterol and LDL were associated with increased risk, while higher HDL tended to reduce risk of AMD. The specific mechanisms underlying the association between AMD and LIPC require further investigation.
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DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
影响因子：
5.2
作者：
Fagerness, Jesen A.;Maller, Julian B.;Seddon, Johanna M.
通讯作者：
Seddon, Johanna M.
影响因子：
13.7
作者：
Hogg, Ruth E.;Woodside, Jayne V.;Chakravarthy, Usha
通讯作者：
Chakravarthy, Usha
影响因子：
30.8
作者：
Kathiresan S;Willer CJ;Peloso GM;Demissie S;Musunuru K;Schadt EE;Kaplan L;Bennett D;Li Y;Tanaka T;Voight BF;Bonnycastle LL;Jackson AU;Crawford G;Surti A;Guiducci C;Burtt NP;Parish S;Clarke R;Zelenika D;Kubalanza KA;Morken MA;Scott LJ;Stringham HM;Galan P;Swift AJ;Kuusisto J;Bergman RN;Sundvall J;Laakso M;Ferrucci L;Scheet P;Sanna S;Uda M;Yang Q;Lunetta KL;Dupuis J;de Bakker PI;O'Donnell CJ;Chambers JC;Kooner JS;Hercberg S;Meneton P;Lakatta EG;Scuteri A;Schlessinger D;Tuomilehto J;Collins FS;Groop L;Altshuler D;Collins R;Lathrop GM;Melander O;Salomaa V;Peltonen L;Orho-Melander M;Ordovas JM;Boehnke M;Abecasis GR;Mohlke KL;Cupples LA
通讯作者：
Cupples LA
影响因子：
56.9
作者：
Edwards, AO;Ritter, R;Farrer, LA
通讯作者：
Farrer, LA