July 2011
Volume 52, Issue 8
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Genetics  |   July 2011
Evaluation of Serum Lipid Concentrations and Genetic Variants at High-Density Lipoprotein Metabolism Loci and TIMP3 in Age-Related Macular Degeneration
Author Affiliations & Notes
  • Sascha Fauser
    From the Department of Vitreoretinal Surgery and
  • Dzenita Smailhodzic
    the Departments of Ophthalmology and
  • Albert Caramoy
    From the Department of Vitreoretinal Surgery and
  • Johannes P.H. van de Ven
    the Departments of Ophthalmology and
  • Bernd Kirchhof
    From the Department of Vitreoretinal Surgery and
    the Cologne Image Reading Center, Center for Ophthalmology, University of Cologne, Cologne, Germany; and
  • Carel B. Hoyng
    the Departments of Ophthalmology and
  • B. Jeroen Klevering
    the Departments of Ophthalmology and
  • Sandra Liakopoulos
    From the Department of Vitreoretinal Surgery and
    the Cologne Image Reading Center, Center for Ophthalmology, University of Cologne, Cologne, Germany; and
  • Anneke I. den Hollander
    the Departments of Ophthalmology and
    Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
  • Corresponding author: A.I. den Hollander, Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Philips van Leydenlaan 15, 6526 EX Nijmegen, the Netherlands; a.denhollander@ohk.umcn.nl
Investigative Ophthalmology & Visual Science July 2011, Vol.52, 5525-5528. doi:10.1167/iovs.10-6827
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      Sascha Fauser, Dzenita Smailhodzic, Albert Caramoy, Johannes P.H. van de Ven, Bernd Kirchhof, Carel B. Hoyng, B. Jeroen Klevering, Sandra Liakopoulos, Anneke I. den Hollander; Evaluation of Serum Lipid Concentrations and Genetic Variants at High-Density Lipoprotein Metabolism Loci and TIMP3 in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(8):5525-5528. doi: 10.1167/iovs.10-6827.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose.: To analyze the association between polymorphisms in the TIMP3 gene and genes of the high-density lipoprotein (HDL) metabolism and age-related macular degeneration (AMD), and evaluate serum lipid and lipoprotein levels in AMD patients compared with control individuals.

Methods.: Single nucleotide polymorphisms in or near the TIMP3, ABCA1, FADS1–3, CETP, LIPC, and LPL genes were genotyped. Serum levels of apolipoprotein B (ApoB), apolipoprotein A2, lipoprotein a, cholesterol, triglycerides, and HDL-cholesterol were determined.

Results.: Significant associations were found between AMD and variants in ABCA1 and FADS1–3, and a nearly significant association in TIMP3. No significant associations were observed for variants in LPL, LIPC, and CETP. We also observed a significant elevation of ApoB levels in serum of AMD patients. Other lipids and lipoproteins were not significantly altered.

Conclusions.: These results confirm associations of AMD with variants near the TIMP3 gene and at loci involved in HDL metabolism. They further highlight a role of the extracellular matrix and the HDL metabolism in the pathogenesis of AMD. This study identified increased ApoB levels as a possible new serum biomarker for AMD.

Age-related macular degeneration (AMD) is a multifactorial disorder caused by genetic and environmental factors. The most consistently identified environmental risk factor is smoking. 1 Despite the late onset of the disease, familial and twin-based studies have shown that AMD has a strong genetic component. 2,3  
Single nucleotide polymorphisms (SNPs) in the complement factor H (CFH) 4 6 gene and in the ARMS2/HTRA1 7 9 gene are strongly associated with AMD. Genetic association studies identified variants in several other genes of the complement pathway such as complement factor B (CFB), 10 component 2 (C2), 10 component 3 (C3), 11 and complement factor I (CFI). 12 Together, these variants account for >50% of the disease risk. 13  
Recently, two genome-wide association studies identified additional genetic markers to be associated with AMD. 14,15 A new susceptibility locus was identified near the TIMP3 gene. 15 TIMP3 is a metalloproteinase involved in degradation of the extracellular matrix. Mutations in TIMP3 are also responsible for an early-onset autosomal dominant macular dystrophy. 16 In addition, loci involved in the high-density lipoprotein (HDL) cholesterol pathway were found to be associated with AMD. Associations were identified with variants in the hepatic lipase (LIPC) gene, the cholesterylester transfer protein (CETP) gene, the ATP-binding cassette transporter A1 (ABCA1) gene, the fatty acid desaturase gene cluster (FADS1–3), and the lipoprotein lipase (LPL) gene. 14,15  
Although these associations point toward a role of the HDL metabolism in AMD, previous studies that have examined the association between serum HDL levels and AMD show conflicting results. 17 23 Some studies found no relationship, 21,23 whereas others found that increased risk of AMD was associated with increased HDL levels 17,19 and yet others have shown an inverse relationship between HDL levels and AMD. 18,20,22 In this study we analyzed these new risk alleles in AMD patients and control individuals from a German/Dutch cohort, to evaluate their relevance in our population. In addition, we evaluated the concentration of lipids and lipoproteins in serum samples of AMD patients and control individuals. 
Material and Methods
Study Population
The European Genetic Database (EUGENDA) is a German/Dutch project studying development and therapy of AMD. In the present study, 1201 AMD patients (827 Dutch and 374 German) and 562 control subjects (476 Dutch and 86 German) from EUGENDA were included. Patients of all AMD stages were included. AMD staging for the EUGENDA study was performed by the Cologne Image Reading Center and Laboratory (CIRCL). Color fundus photographs of both eyes of all cases were evaluated by two independent reading center graders according to the standard protocol of the Cologne Image Reading Center and Laboratory. AMD was defined as the presence of at least 10 small, hard drusen and pigmentary changes, or at least one intermediate size druse. Control individuals exhibited no signs of AMD in either eye and showed no other macular pathology. Data of AMD cases and control individuals of similar ages were collected, although the mean age of AMD patients (75.86 ± 8.16 years) was slightly higher than that of the control individuals (72.72 ± 6.63 years). All individuals were from the Nijmegen (Netherlands) and Cologne (Germany) area, respectively. The research protocols followed the tenets of the Declaration of Helsinki. All participants provided written informed consent. The protocols were reviewed and approved by the local institutional review boards. 
Genotyping and Lipid/Lipoprotein Measurements
Genomic DNA was extracted from peripheral blood samples using standard procedures. Genotyping of SNPs in the TIMP3 (rs9621532), LIPC (rs10468017), LPL (rs12678919), ABCA1 (rs1883025), FADS1–3 (rs174547), and CETP (rs3764261) genes was carried out as previously described. 24 Serum levels of apolipoprotein B (ApoB), apolipoprotein A2 (ApoA2), lipoprotein a (Lpa), cholesterol, triglycerides, and HDL-cholesterol (HDLC) were measured in a subset of patients and controls using standard procedures by a clinical chemistry laboratory (Architect Analyzer; Abbott Diagnostics Hoofddorp, the Netherlands). 
Statistical Analysis
Differences between case and control subjects in baseline characteristics, mean serum lipid and lipoprotein levels, and risk allele frequencies were tested using the χ2 or Student's t-test, where appropriate. Linear regression was performed to determine whether genotypes in LIPC, LPL, ABCA1, FADS1–3, and CETP are associated with ApoB and triglyceride levels. Reported P values are two-sided and considered statistically significant if <0.05. Statistical analyses were performed using statistical software (SPSS, version 16.0; IBM, Armonk, NY). 
Results
Baseline demographics of the Dutch-German cohort are shown in Table 1. The mean age of the AMD patients is slightly higher than in the control individuals. Female sex and current smoking status were significantly associated with AMD. 
Table 1.
 
Baseline Characteristics and Mean Lipid/Lipoprotein Levels in AMD Cases and Control Individuals
Table 1.
 
Baseline Characteristics and Mean Lipid/Lipoprotein Levels in AMD Cases and Control Individuals
Control AMD P
n 562 1201
Female, % 56.2 62.0 0.020
Age (mean), y 72.72 ± 6.63 75.86 ± 8.16 <0.001
Smoking n = 472 n = 734
    Never, % 40.7 42.9
    Past, % 53.6 45.1 0.068
    Current, % 5.7 12.0 0.004
BMI (mean) n = 452; 25.92 ± 3.90 n = 717; 25.96 ± 4.06 0.867
ApoB, mg/L n = 398; 979 ± 227 n = 689; 1012 ± 251 0.029
ApoA2, mg/L n = 398; 1610 ± 313 n = 690; 1615 ± 304 0.802
Lpa, U/L* n = 397; 164 ± 350 n = 691; 168 ± 386 0.983
Cholesterol, mM/L n = 521; 5.88 ± 1.18 n = 792; 5.93 ± 1.27 0.425
Triglycerides, mM/L n = 521; 1.92 ± 0.95 n = 780; 1.90 ± 1.05 0.661
HDLC, mM/L n = 521; 1.44 ± 0.36 n = 805; 1.46 ± 0.37 0.327
The risk allele distributions were analyzed in the Dutch-German cohort (Table 2). The risk allele frequency of rs1883025 in the ABCA1 gene was significantly higher in AMD patients compared with control individuals (P = 0.00027). The risk allele frequency of rs174547 in the FADS1–3 gene was significantly elevated in AMD patients in the combined cohorts (P = 0.015). A nearly significant association was observed for rs9621532 in the TIMP3 gene (P = 0.067). We did not find significant associations for SNPs in the LPL, LIPC, and CETP genes. 
Table 2.
 
Risk Allele Frequencies in AMD Cases and Control Individuals
Table 2.
 
Risk Allele Frequencies in AMD Cases and Control Individuals
Gene SNP Alleles (Risk/Nonrisk) Controls AMD OR (95% CI) P
TIMP3 rs9621532 A/C 0.953 0.966 1.41 (0.98–2.03) 0.067
LIPC rs10468017 C/T 0.698 0.711 1.07 (0.91–1.25) 0.442
LPL rs12678919 G/A 0.098 0.097 0.98 (0.77–1.26) 0.879
ABCA1 rs1883025 C/T 0.729 0.786 1.36 (1.15–1.61) 2.7 × 10−4
FADS1–3 rs174547 T/C 0.654 0.696 1.21 (1.04–1.41) 0.015
CETP rs3764261 A/C 0.314 0.342 1.14 (0.97–1.33) 0.108
Mean (or median) serum levels of ApoB, ApoA2, Lpa, cholesterol, triglycerides, and HDLC in AMD patients and control individuals are presented in Table 1. Mean ApoB levels were significantly higher in AMD patients (1012 ± 521 mg/L) than in control individuals (979 ± 227 mg/L) in the Dutch-German cohort. No significant associations were found for the other lipids and lipoproteins. 
ApoB levels were higher in individuals carrying the homozygous high-risk CC genotype (1007 ± 241 mg/L) compared with individuals carrying the homozygous low-risk TT genotype (940 ± 222 mg/L; Table 3). The mean ApoB levels increased with the number of risk alleles in ABCA1 (P = 0.041), but this finding did not remain significant after adjusting for age and sex (P = 0.061). 
Table 3.
 
Association between ApoB Levels and Number of Risk Alleles at HDL Loci
Table 3.
 
Association between ApoB Levels and Number of Risk Alleles at HDL Loci
Gene Risk Allele Mean ApoB Levels in Individuals P P *
Carrying No Risk Alleles Carrying One Risk Allele Carrying Two Risk Alleles
LIPC C 992 ± 241 998 ± 233 1002 ± 254 0.683 0.477
LPL G 994 ± 243 1001 ± 231 1156 ± 390 0.126 0.208
ABCA1 C 940 ± 222 989 ± 245 1007 ± 241 0.041 0.061
FADS1–3 T 1005 ± 237 983 ± 241 1008 ± 240 0.364 0.364
CETP A 995 ± 250 994 ± 232 1004 ± 248 0.817 0.762
Discussion
In this case-control study we confirmed the presence of associations between AMD and polymorphisms at loci of the HDL metabolism: ABCA1 and FADS1–3. Furthermore, we observed a nearly significant association with a polymorphism near the TIMP3 gene. However, no association was observed for SNPs in the LIPC, LPL, and CETP genes. Lack of association has also been observed in other cohorts; e.g., the previously reported association with the variant in the LIPC gene was not identified in two of seven cohorts studied. 14 This suggests that these variants may be differentially distributed among different populations. Alternatively, our study may not have sufficient power to detect modest effects; in particular for the LIPC and LPL SNPs the effect in our cohort seems to be more modest than previously described in other cohorts. 
We detected elevated serum ApoB levels in AMD patients compared with control individuals. The serum levels of other lipids and lipoproteins, including HDLC, did not differ significantly between AMD cases and control individuals. 
These data add further support that several pathways contribute to the pathogenesis of AMD. Besides the well-established involvement of the complement system (CFH, C2, C3, CFB), 25 additional genes encoding components of the extracellular matrix (ARMS2 and TIMP3), 15,26 and genes of HDL metabolism play a role in the pathogenesis of AMD. Although the genes involved in HDL metabolism have a relatively small contribution to the development of AMD, they may reveal novel pharmacological targets to prevent AMD in individuals carrying high-risk alleles in these genes. 
TIMP3 inhibits matrix metalloproteinase (MMP) and is involved in degradation of the extracellular matrix. It can also inhibit vascular endothelial factor (VEGF)-mediated angiogenesis independent of its matrix metalloproteinase-inhibitory activity. 27 Mutations in this gene can cause Sorsby fundus dystrophy, an autosomal dominant macular dystrophy with clinical features similar to AMD and an early onset before 40 years. Both TIMP3 and ARMS2 seem to be involved in extracellular matrix function. It has been shown that ARMS2 interacts with several matrix proteins. 26 This highlights the important role of the extracellular matrix in the pathogenesis of AMD. 
This study supports previous associations between AMD and HDL metabolism. 14,15 It is unclear how polymorphisms in genes of HDL metabolism can influence the development of AMD. Changes in HDL levels may lead to the accumulation of cholesterol and lipids in drusen. There has been some confusion because some alleles increase HDL levels and decrease the risk for AMD, while other alleles decrease HDL levels and increase the risk for AMD. 14,15 Studies on the association between plasma HDL levels and AMD are also inconsistent. Studies have found no relationship, 21 a relationship between increased 17,19 and decreased HDL levels 20,22,28 and AMD. In a recent study by Reynolds et al., elevated HDL levels in AMD were found to be associated with the LIPC genotype. 28 In this study, we did not observe altered serum HDL levels in AMD, nor did we find an association with ApoA2, Lpa, cholesterol, and triglyceride levels, despite that our study cohort was significantly larger and thus has more power than previous case-control studies. 20,21,28  
In this study we did find significantly elevated serum ApoB levels in AMD patients compared with controls, which may partially be explained by the ABCA1 risk allele. A previous study also observed a marked increase of ApoB levels in AMD patients. 20 ApoB is a major low-density lipoprotein (LDL) transporting cholesterols to tissues. High levels of ApoB have been associated with atherosclerosis. 29 ABCA1 is known as the key transporter that facilitates this initial step in reverse cholesterol transport. In transgenic mice, ABCA1 overexpression raised plasma ApoB levels by delayed 125I-apoA-I catabolism without altering ApoB secretion. 30 In AMD, lipids accumulate in Bruch membrane, a process which may be mediated through ABCA1. Transgenic mice overexpressing ApoB in the retinal pigment epithelium develop a phenotype similar to early human AMD. 31 Elevated levels of ApoB lipoproteins are known to stimulate inflammation although the underlying etiology of chronic subclinical inflammation is not clear. 32 This may be another possible mode of action of lipoproteins in the pathogenesis of AMD. 
In conclusion, these results confirm associations of AMD and the loci for TIMP3 and genes of HDL metabolism: ABCA1 and FADS1–3. They further stress the role of the extracellular matrix and the HDL metabolism in the pathogenesis of AMD. Our study did not detect elevated HDL levels in AMD, but identified increased ApoB levels as a possible new serum biomarker for AMD. 
Footnotes
 Supported by the Netherlands Organisation for Scientific Research (Grant 016.096.309), MD fonds, Oogfonds, Landelijke Stichting voor Blinden en Slechtzienden, Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, Stichting Researchfonds Oogheelkunde, Stichting Nederlands Oogheelkundig Onderzoek, Stichting Blindenhulp, Gelderse Blindenstichting, Forschung für das Sehen, and Retinovit Stiftung.
Footnotes
 Disclosure: S. Fauser, None; D. Smailhodzic, None; A. Caramoy, None; J.P.H. van de Ven, None; B. Kirchhof, None; C.B. Hoyng, None; B.J. Klevering, None; S. Liakopoulos, None; A.I. den Hollander, None
The authors thank Johannes M.M. Groenewoud, Bert Janssen, Tiny Janssen-van Kempen, Frederieke Schoenmaker-Koller, and Agnes de Vries for excellent technical assistance. 
References
Montezuma SR Sobrin L Seddon JM . Review of genetics in age related macular degeneration. Semin Ophthalmol. 2007;22:229–240. [CrossRef] [PubMed]
Seddon JM Ajani UA Mitchell BD . Familial aggregation of age-related maculopathy. Am J Ophthalmol. 1997;123:199–206. [CrossRef] [PubMed]
Seddon JM Cote J Page WF Aggen SH Neale MC . The US twin study of age-related macular degeneration: relative roles of genetic and environmental influences. Arch Ophthalmol. 2005;123:321–327. [CrossRef] [PubMed]
Haines JL Hauser MA Schmidt S . Complement factor H variant increases the risk of age-related macular degeneration. Science. 2005;308:419–421. [CrossRef] [PubMed]
Hageman GS Anderson DH Johnson LV . A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci U S A. 2005;102:7227–7232. [CrossRef] [PubMed]
Klein RJ Zeiss C Chew EY . Complement factor H polymorphism in age-related macular degeneration. Science. 2005;308:385–389. [CrossRef] [PubMed]
Rivera A Fisher SA Fritsche LG . Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk. Hum Mol Genet. 2005;14:3227–3236. [CrossRef] [PubMed]
Yang Z Camp NJ Sun H . A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science. 2006;314:992–993. [CrossRef] [PubMed]
Dewan A Liu M Hartman S . HTRA1 promoter polymorphism in wet age-related macular degeneration. Science. 2006;314:989–992. [CrossRef] [PubMed]
Gold B Merriam JE Zernant J . Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat Genet. 2006;38:458–462. [CrossRef] [PubMed]
Yates JR Sepp T Matharu BK . Complement C3 variant and the risk of age-related macular degeneration. N Engl J Med. 2007;357:553–561. [CrossRef] [PubMed]
Fagerness JA Maller JB Neale BM Reynolds RC Daly MJ Seddon JM . Variation near complement factor I is associated with risk of advanced AMD. Eur J Hum Genet. 2009;17:100–104. [CrossRef] [PubMed]
Maller J George S Purcell S . Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration. Nat Genet. 2006;38:1055–1059. [CrossRef] [PubMed]
Neale BM Fagerness J Reynolds R . Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC). Proc Natl Acad Sci U S A. 2010;107:7395–7400. [CrossRef] [PubMed]
Chen W Stambolian D Edwards AO . Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. Proc Natl Acad Sci U S A. 2010;107:7401–7406. [CrossRef] [PubMed]
Weber BH Vogt G Pruett RC Stohr H Felbor U . Mutations in the tissue inhibitor of metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy. Nat Genet. 1994;8:352–356. [CrossRef] [PubMed]
van Leeuwen R Tomany SC Wang JJ . Is medication use associated with the incidence of early age-related maculopathy? Pooled findings from 3 continents. Ophthalmology. 2004;111:1169–1175. [CrossRef] [PubMed]
Wachter A Sun Y Dasch B Krause K Pauleikhoff D Hense HW . Munster age- and retina study (MARS). Association between risk factors for arteriosclerosis and age-related macular degeneration [in German]. Ophthalmologe. 2004;101:50–53. [CrossRef] [PubMed]
Delcourt C Michel F Colvez A Lacroux A Delage M Vernet MH . Associations of cardiovascular disease and its risk factors with age-related macular degeneration: the POLA study. Ophthalmic Epidemiol. 2001;8:237–249. [CrossRef] [PubMed]
Nowak M Swietochowska E Marek B . Changes in lipid metabolism in women with age-related macular degeneration. Clin Exp Med. 2005;4:183–187. [CrossRef] [PubMed]
Abalain JH Carre JL Leglise D . Is age-related macular degeneration associated with serum lipoprotein and lipoparticle levels? Clin Chim Acta. 2002;326:97–104. [CrossRef] [PubMed]
Tan JS Mitchell P Smith W Wang JJ . Cardiovascular risk factors and the long-term incidence of age-related macular degeneration: the Blue Mountains Eye Study. Ophthalmology. 2007;114:1143–1150. [CrossRef] [PubMed]
Risk factors for neovascular age-related macular degeneration. The Eye Disease Case-Control Study Group. Arch Ophthalmol. 1992;110:1701–1708. [CrossRef] [PubMed]
Hawkins JR Khripin Y Valdes AM Weaver TA . Miniaturized sealed-tube allele-specific PCR. Hum Mutat. 2002;19:543–553. [CrossRef] [PubMed]
Anderson DH Radeke MJ Gallo NB . The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited. Prog Retin Eye Res. 2010;29:95–112. [CrossRef] [PubMed]
Kortvely E Hauck SM Duetsch G . ARMS2 is a constituent of the extracellular matrix providing a link between familial and sporadic age-related macular degenerations. Invest Ophthalmol Vis Sci. 2010;51:79–88. [CrossRef] [PubMed]
Qi JH Ebrahem Q Moore N . A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med. 2003;9:407–415. [CrossRef] [PubMed]
Reynolds R Rosner B Seddon JM . Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration. Ophthalmology. 2010;117:1989–1995. [CrossRef] [PubMed]
Weissglas-Volkov D Pajukanta P . Genetic causes of high and low serum HDL-cholesterol. J Lipid Res. 2010;51:2032–2057. [CrossRef] [PubMed]
Vaisman BL Lambert G Amar M . ABCA1 overexpression leads to hyperalphalipoproteinemia and increased biliary cholesterol excretion in transgenic mice. J Clin Invest. 2001;108:303–309. [CrossRef] [PubMed]
Fujihara M Bartels E Nielsen LB Handa JT . A human apoB100 transgenic mouse expresses human apoB100 in the RPE and develops features of early AMD. Exp Eye Res. 2009;88:1115–1123. [CrossRef] [PubMed]
Fan J Watanabe T . Inflammatory reactions in the pathogenesis of atherosclerosis. J Atheroscler Thromb. 2003;10:63–71. [CrossRef] [PubMed]
Table 1.
 
Baseline Characteristics and Mean Lipid/Lipoprotein Levels in AMD Cases and Control Individuals
Table 1.
 
Baseline Characteristics and Mean Lipid/Lipoprotein Levels in AMD Cases and Control Individuals
Control AMD P
n 562 1201
Female, % 56.2 62.0 0.020
Age (mean), y 72.72 ± 6.63 75.86 ± 8.16 <0.001
Smoking n = 472 n = 734
    Never, % 40.7 42.9
    Past, % 53.6 45.1 0.068
    Current, % 5.7 12.0 0.004
BMI (mean) n = 452; 25.92 ± 3.90 n = 717; 25.96 ± 4.06 0.867
ApoB, mg/L n = 398; 979 ± 227 n = 689; 1012 ± 251 0.029
ApoA2, mg/L n = 398; 1610 ± 313 n = 690; 1615 ± 304 0.802
Lpa, U/L* n = 397; 164 ± 350 n = 691; 168 ± 386 0.983
Cholesterol, mM/L n = 521; 5.88 ± 1.18 n = 792; 5.93 ± 1.27 0.425
Triglycerides, mM/L n = 521; 1.92 ± 0.95 n = 780; 1.90 ± 1.05 0.661
HDLC, mM/L n = 521; 1.44 ± 0.36 n = 805; 1.46 ± 0.37 0.327
Table 2.
 
Risk Allele Frequencies in AMD Cases and Control Individuals
Table 2.
 
Risk Allele Frequencies in AMD Cases and Control Individuals
Gene SNP Alleles (Risk/Nonrisk) Controls AMD OR (95% CI) P
TIMP3 rs9621532 A/C 0.953 0.966 1.41 (0.98–2.03) 0.067
LIPC rs10468017 C/T 0.698 0.711 1.07 (0.91–1.25) 0.442
LPL rs12678919 G/A 0.098 0.097 0.98 (0.77–1.26) 0.879
ABCA1 rs1883025 C/T 0.729 0.786 1.36 (1.15–1.61) 2.7 × 10−4
FADS1–3 rs174547 T/C 0.654 0.696 1.21 (1.04–1.41) 0.015
CETP rs3764261 A/C 0.314 0.342 1.14 (0.97–1.33) 0.108
Table 3.
 
Association between ApoB Levels and Number of Risk Alleles at HDL Loci
Table 3.
 
Association between ApoB Levels and Number of Risk Alleles at HDL Loci
Gene Risk Allele Mean ApoB Levels in Individuals P P *
Carrying No Risk Alleles Carrying One Risk Allele Carrying Two Risk Alleles
LIPC C 992 ± 241 998 ± 233 1002 ± 254 0.683 0.477
LPL G 994 ± 243 1001 ± 231 1156 ± 390 0.126 0.208
ABCA1 C 940 ± 222 989 ± 245 1007 ± 241 0.041 0.061
FADS1–3 T 1005 ± 237 983 ± 241 1008 ± 240 0.364 0.364
CETP A 995 ± 250 994 ± 232 1004 ± 248 0.817 0.762
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