Association of Genes in the High-Density Lipoprotein Metabolic Pathway with Polypoidal Choroidal Vasculopathy in Asian Population: A Systematic Review and Meta-Analysis
Journal of Ophthalmology
Association of Genes in the High-Density Lipoprotein Metabolic Pathway with Polypoidal Choroidal Vasculopathy in Asian Population: A Systematic Review and Meta-Analysis
Ming-zhen Yuan 0
Ruo-an Han 0
Chen-xi Zhang 0
You-xin Chen 0
0 Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China
Purpose. To assess the association of genes in the high-density lipoprotein metabolic pathway (HDLMP) with polypoidal choroidal vasculopathy (PCV) and the genetic difference in the HDLMP between PCV and age-related macular degeneration (AMD). Methods. We performed a literature search in EMBASE, PubMed, and Web of Science for genetic studies on 7 single nucleotide polymorphisms (SNPs) from 5 genes in the HDLMP including cholesteryl ester transfer protein (CETP), hepatic lipase (LIPC), lipoprotein lipase (LPL), ATP-binding cassette transporter A1 (ABCA1), and ATP-binding cassette transporter G1 (ABCG1) in PCV. All studies were published before September 30, 2017, without language restriction. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) of each polymorphism were estimated. We also compared the association profiles between PCV and AMD and performed a sensitivity analysis. Results. Our result is based on 43 articles. After excluding duplicates and articles without complete information, 7 studies were applicable to meta-analysis. 7 polymorphisms were meta-analyzed: CETP rs2303790/rs3764261, LIPC rs10468017/rs493258, LPL rs12678919, ABCA1 rs1883025, and ABCG1 rs57137919. We found that in Asian population, CETP rs3764261 (T allele; OR 1.46; 95% CI: 1.28-1.665, P < 0.01), CETP rs2303790 (G allele; OR 1.57; 95% CI: 1.258-1.96, P < 0.01), and ABCG1 rs57137919 (A allele; OR 1.168; 95% CI: 1.016-1.343, P < 0.01) were significantly associated with PCV, and ABCG1 rs57137919 (A allele; OR 1.208, 95% CI: 1.035-1.411, P < 0.01) has different effects in PCV and AMD. -e other 4 polymorphisms in LIPC/LPL/ABCA1 had no significant association with PCV (P > 0.05). -e sensitivity analysis validated the significance of our analysis. Conclusions. Our study revealed 7 polymorphisms in 5 genes. Among them, CETP (rs3764261/rs2303790) and ABCG1 (rs57137919) were the major susceptibility genes for PCV in Asian population and ABCG1 (rs57137919) showed allelic diversity between PCV and AMD. Since the size for PCV and AMD was small, we need to study these genes genotyping in larger samples.
Polypoidal choroidal vasculopathy (PCV) is a choroidal
vascular disease of first described in the early 1980s as
polypoidal subretinal vascular lesions associated with serous
or hemorrhagic detachment of the retinal pigment
epithelium (RPE) [
]. Later, PCV is regarded as a particular type of
choroidal neovascularization (CNV) characterized by the
distinct presence of polypoidal vascular lesions and a branching
vascular network. PCV can be clearly demonstrated and
diagnosed by indocyanine green angiography [
a clinical perspective, PVC is considered as a subtype of
AMD because of some similarities like neovascularization,
subretinal hemorrhage and fluid, pigment epithelial
detachment (PED), vision loss owing to bleeding, leakage, scar
formation, and other similarities in phenotypic features
]. Genetically, PCV and AMD also have the common
susceptible genes, such as high temperature required factor
A1 gene (HTRA1) and the complementary factor H gene
(CFH) . However, many controversial studies demonstrate
that PCV should be classified as a distinct disease entity of
AMD for their different epidemiological, clinical
characteristics, natural history, and treatment outcomes [
Moreover, recent researches in the field of genetics suggest that
PCV may not be as closely related to AMD, such as its
differential risk to a mutation in FGD6, viralicidic activity 2-like
(SKIV2L), complement component 3 (C3), elastin (ELN), and
apolipoprotein E (APOE) [
]. -ese literatures make for
a question whether PCV is a subtype of AMD or a distant
disease from AMD.
Many studies have indicated lipid deposition in Bruch?s
membrane and soft drusen, and the amount of lipid was
lower in the peripheral area than in the macula of human
]. A number of population-based studies revealed the
association between drusen and the AMD, and drusen are
regarded as one of the determinant factors of both early and
late AMD [
]. In addition, some studies indicated that
the prevalence of drusen under RPE was lower in PCV than
in AMD [
], which pointed out that absence of drusen
may be one of the important criteria to diagnose PCV.
However, some clinical studies insisted that drusen were
frequently seen in PCV [
], and several studies reported
that drusen were observed in 20% to 27% of unaffected
]. -erefore, whether drusen plays a functional role in
the occurrence and development is still up for debate. As we
know, lipids stand for over 40% of the drusen volume [
therefore, many academics studied the vital function of
lipids in the pathogenesis of PCV and AMD. Due to the
different ethnic groups and lifestyles of individuals, the
strength of such relevances is widely variable [
therefore, many studies investigated the effect between gene
variations in the HDLMP and risk factors on PCV and
AMD. Genetic studies in the HDLMP with PCV and AMD
have identified susceptibility single nucleotide polymorphisms
(SNPs) in multiple genes, including rs3764261/rs2303790 in
CETP, rs493258/rs10468017 in LIPC, rs12678919 in LPL,
rs1883025 in ABCA1, and rs57137919 in ABCG1.
-us far, some studies have studied the impact of lipid
metabolism-related and systemic lipoprotein genes in PCV.
Here, in order to give the comprehensive analysis of effects and
solve the controversies, we conduct meta-analysis and report
a systematic review by summing up all published articles of
genetic associations in the HDLMP of PCV. -is study (1)
conducted an investigation of which genetic variants of the
HDLMP are meaningfully associated with PCV and their
effect sizes and (2) analyzed whether there were differences
between genetic risks of the HDLMP in PCV and AMD.
2.1. Search Strategy. We searched EMBASE, PubMed, and
Web of Science using the following MeSH terms and free
words: (polypoidal choroidal vasculopathy or polypoidal
choroidal vascular disease or polypoidal choroidal vascular
diseases or PCV) and (cholesteryl ester transfer protein or
CETP or hepatic lipase or LIPC or lipoprotein lipase or LPL
or ATP-binding cassette transporter A1 or ABCA1 or
ATPbinding cassette transporter G1 or ABCG1). All searched
articles were published before September 30, 2017, without
language restriction. We also screened the reference lists of
all eligible studies, reviews, and meta-analyses to ensure that
any relevant studies were not omitted. We also searched all
reported genome-wide association studies of PCV including
the supplementary materials to maximize the usable data.
-e detail of search strategy is revealed in Table S1.
2.2. Inclusion and Exclusion Criteria. We included those
studies that satisfied the following criteria in the meta-analysis:
(1) case-control studies, cohort studies, or population-based
studies that evaluated the association of gene variants of
CETP/LIPC/LPL/ABCA1/ABCG1 with PCV or its subtypes
and (2) allele or genotype counts and/or frequencies being
presented or able to be calculated from the data in the study.
Case reports, conference reports, reviews, animal studies, and
reports with insufficient information were excluded (Table S2).
2.3. Data Extraction and Quality Assessment. Two reviewers
(Y. M. z. and Y. J. y.) independently reviewed and
extracted data from studies on the association between
CETP/LIPC/LPL/ABCA1/ABCG1 SNPs and PCV. If there
were any differences between them, another two reviewers
would help to resolve it (Z. C. x. and H. R. a.) after thorough
discussion. -e following information was extracted from each
article: the name of first author, publication year, ethnicity of
the study population, study design, genotyping method,
sample size, demographics, allele and genotype distribution
(Table 1), and the results of the Hardy?Weinberg equilibrium
(HWE) test in controls (Table S3). We assessed the quality of
individual studies using the Newcastle?Ottawa Scale [
Briefly, 9 quality indicators were used; if a study fulfilled 1
indicator, we assigned a ?yes? under this item or a ?no.? -us,
the quality score for each study might be between 0 and 9
2.4. Statistical Analysis. We conducted meta-analysis for each
polymorphism which had been reported in ?2 studies or
cohorts. -e association was evaluated by different genetic
models, including allelic, heterozygous, and homozygous
models. For each study, the odds ratio (OR) with 95%
confidence interval (95% CI) was calculated to evaluate the
strength of association between the each SNP and PCV risk.
Moreover, we used the I2 value to quantify the proportion of
the variability in effect estimates, which is due to heterogeneity
rather than sampling error. -e I2 value was shown as of no
(0?25%), low (25?50%), moderate (50?75%), or high
heterogeneity (75?100%) [
]. -e I2 test was to assess
heterogeneity among studies. -e potential publication bias was
assessed visually in a funnel plot of log (OR) against its standard
error, and the degree of asymmetry was evaluated using Begg?s
test and Egger?s test (P < 0.05 was considered to be statistically
significant). We undertook the sensitivity analysis to examine
the influence by removing the unreliable study [
software STATA (version 12.0, StataCorp LP, College Station,
TX) was used for the meta-regression analysis. A pooled P
value of less than 0.05 was considered statistically significant.
3.1. Eligibility and Characteristics of Included Studies.
Figure 1 illustrates the study inclusion of this meta-analysis.
A total of 43 articles published before September 30, 2017,
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16 articles identified
10 articles identified
Web of Science:
17 articles identified
23 independent studies
20 duplicates excluded
16 records were excluded:
4 conference abstracts
1 not separate PCV from AMD
1 not case-control study
7 articles were finally included in the meta-analysis
were identi ed in the EMBASE, PubMed, and Web of
Science databases. Of these, we excluded 20 articles because
they were duplicates. For the remaining 23 studies, the full
texts were retrieved. After reviewing the full texts, we
excluded another 16 reports, among which 5 studies were
reviews, 4 were not related to PCV, 4 were conference
abstracts, 1 was not about the genetic studies, 1 did not
separate PCV from AMD, and 1 was not the case-control
study. Finally, 7 articles were eligible for the meta-analysis
], involving 3342 PCV cases versus 8256 controls and
2761 PCV cases versus 2660 AMD cases. ?e main traits of
the included studies are summed up in Table 1. Patients from
each study received complete ophthalmic examinations,
including ?uorescein angiography and ICGA. Polypoidal
choroidal vasculopathy was diagnosed on the basis of
choroidal polypoidal lesions shown by ICGA. All studies
adopted a case-control design. ?ese studies were performed
in various populations, including Chinese (6 studies),
Japanese (3 studies), and Korean (1 study). In all studies, valid
genotyping approaches were used, including polymerase
chain reaction, TaqMan genotyping assay, and BeadChip.
3.2. Risk of Bias Assessment in Eligible Studies. As shown in
Table S4, all eligible studies clearly described the diagnostic
criteria for PCV and AMD. Patients with other macular
diseases like central serous chorioretinopathy, myopic
choroidal neovascularization, angioid streaks, presumed ocular
histoplasmosis, or with CNV and PCV in the same or fellow
eye were excluded. In all studies, comprehensive ophthalmic
examinations were performed on the control subjects. One
study used control subjects recruited from the community
], and the others used hospital-recruited controls. Two
studies were diverse-ethnic population study [
study did not provide the sex and age of cohorts. ?ere was no
ethnic di?erence between cases and controls. Confounding
factors were matched between cases and controls in 7 studies.
?e scores for the quality assessment ranged from 5 to 7. All
the studies informed HWE in controls.
3.3. Meta-Analysis of CETP/LIPC/LPL/ABCA1/ABCG1
Polymorphisms in PCV. Totally 17 SNPs had been studied
in PCV in the literature (Figure 2). However, only 7 SNPs
(CETP rs2303790/rs3764261, LIPC rs10468017/rs493258, LPL
rs12678919, ABCA1 rs1883025, and ABCG1 rs57137919) in
PCV were reported in more than one study and thus eligible
for meta-analysis (details can be seen in Table S5). Summary of
the allelic associations of these polymorphisms is shown in
Table 2. ?e other 10 SNPs reported in only one report but
performed no association with PCV [
CETP rs3764261 is the most widely investigated SNP in
PCV, with a number of 1355 cases and 1493 controls studied
for the meta-analysis [
32, 33, 35, 36
]. ?e results showed
statistically signi cant association between CETP rs3764261
and PCV in Asian population (Table 2). As for the allelic
model, the odds ratio (OR) for the risk allele T was 1.46 (95%
con dence interval (CI): 1.28?1.665, P < 0.01, I2 0%). In
the subgroup analysis by ethnicity, still signi cant
association was detected in Chinese (OR 1.528, 95% CI: 1.268?
1.841, P < 0.01, I2 0%). Also, CETP rs2303790 [
ABCG1 rs57137919 [35, 37] showed signi cant associations
with PCV in the allelic model. As for CETP rs2303790, the
frequency of the G allele was signi cantly higher in PCV
patients than in controls, conferring a 1.57-fold increased
risk toward PCV (95% CI: 1.258?1.96, P < 0.01, I2 0). As for
ABCG1 rs57137919, the frequency of the A allele was sig
ni cantly higher in PCV patients than in controls,
conferring a 1.168-fold increased risk (95% CI: 1.016?1.343,
P 0.029, I2 61.5%). ?rough quality assessment and
sensitivity analysis, we found the heterogeneity derived from
the data of Shantou population [
]. After excluding the data
of Shantou population, the result showed that the pooled
allelic OR was signi cantly elevated (A allele; OR 1.313,
Heterogeneity chi-squared = 0.13 (d.f = 2) p = 0.939
I-squared (variation in OR attributable to heterogeneity) = 0.0%
Test of OR = 1 : z = 0.57 p = 0.565
Zhang et al.  (Chinese)
Heterogeneity chi-squared = 9.16 (d.f. = 2) p = 0.10
I-squared (variation in OR attributable to heterogeneity) = 78.2%
Test of OR = 1: z = 0.41 p = 0.679
Nakata et al.  (Japanese)
95% CI: 1.113?1.548, P < 0.01, I2 0%). Regarding the other
4 SNPs, LIPC rs10468017/rs493258, LPL rs12678919, and
ABCA1 rs1883025, the pooled ORs were not statistically
signi cant in PCV in the allelic (P > 0.05). As for ABCA1
rs1883025 (T allele; OR 0.968, 95% CI: 0.828?1.131,
P 0.679, I2 78.2%), quality assessment and sensitivity
analysis showed that the study of Zhang et al. was of higher
risk of causing bias than the other cohorts [
we excluded the study and also found that the pooled allelic
OR was not signi cant (T allele; OR 1.1, 95% CI: 0.926?
1.335, P 0.257, I2 0%).
3.4. Meta-Analysis of CETP/LIPC/LPL/ABCA1/ABCG1
Polymorphisms Compared between PCV and AMD. We
identi ed 6 studies in which both PCV and AMD were
assessed for associations with a total of 7 SNPs in 5 genes
(i.e., CETP rs2303790/rs3764261, LIPC rs10468017/rs493258,
LPL rs12678919, ABCA1 rs1883025, and ABCG1 rs57137919)
(Table 3 and Figure 3). Only 1 SNP (ABCG1 rs57137919)
showed signi cant di?erence between PCV and AMD (A allele;
OR 1.208, 95% CI: 1.035?1.411, P 0.017, I2 0%) [
?e other 6 SNPs, namely, CETP rs2303790/rs3764261, LIPC
rs10468017/rs493258, LPL rs12678919, and ABCA1 rs1883025,
Summary of the genetic difference in CETP/LIPC/LPL/ABCA1/ABCG1 polymorphisms between PCV and AMD is shown. PCV: polypoidal choroidal
vasculopathy; AMD: age-related macular degeneration; OR: odds ratio; CI: confidence interval.
were evaluated in 2 to 3 cohorts and showed no significant
differences between PCV and AMD (P > 0.05). As for CETP
rs3764261 (T allele; OR 1.17, 95% CI: 0.971?1.409, P 0.178,
I2 33.6%), quality assessment and sensitivity analysis showed
that the study of Liu et al. was of higher risk of causing bias than
the other cohorts . -erefore, we ruled out the cohort, and
then the pooled allelic OR of the result was significant (T allele;
OR 1.301, 95% CI: 1.033?1.638, P 0.025, I2 0%) [
3.5. Publication Bias Analysis. In theory, due to the limited
number of available studies, it is not suitable for publication
bias analysis. But in order to make this meta-analysis more
powerful and more creditable, we used funnel plots and
Begg?s/Egger?s test to detect publication bias. Begg?s test and
Egger?s test suggested an absence of publication bias in the
all SNPs (P > 0.05) (Tables 2 and 3). -e shape of the funnel
plots did not reveal any evidence of obvious asymmetry
(Figures S1 and S2).
In the systematic review and meta-analysis, we have
summarized the association profiles of genes in the HDLMP in
PCV and assessed the genetic difference in the HDLMP
between PCV and AMD for the first time (i.e., CETP, LIPC,
LPL, ABCA1, and ABCG1). We found significant association
between reported CETP rs2303790/rs3764261, ABCG1
rs57137919, and PCV. Also, we identified ABCG1 rs57137919
showing significant differences between PCV and AMD. In
contrast, LIPC rs10468017/rs493258, LPL rs12678919, and
ABCA1 rs1883025 were not statistically significant in PCV
and reported SNPs in 4 genes in the HDLMP (i.e., CETP,
LIPC, LPL, and ABCA1) showed no significant differences
between PCV and AMD.
CETP can make oxidized lipids transfer from the outer
segments of the photoreceptors or other membranes to
HDL-like lipoprotein particles. -e particles are internalized
by RPE and excreted back into the circulation via ABCG1
transporters through Bruch?s membrane [
]. ABCG1 was
relevant to an increased macrophage apoptosis, which may
be due to the accumulation of oxysterol in macrophages
caused by decreased ABCG1-mediated cholesterol efflux
]. ABCA1 was expressed in the retina and retinal pigment
], and ABCA1 can form nascent HDL by
mediating the efflux of cholesterol and phospholipids to
lipid-poor apolipoproteins [
]. Also, several studies
have demonstrated ABCA1 was significantly related to the
progression of drusen, but the association between large
drusen and geographic atrophy/neovascular was not
significant . Besides, LIPC gene is a critical enzyme in HDL
metabolism which has the function of encoding hepatic
triglyceride lipase and catalyzing the hydrolysis of
phospholipids, monoglycerides, diglycerides, triglycerides, and
acylCoA thioesters [
]. LPL gene encodes LPL which
can play an important role in HDL metabolism. LPL can not
only facilitate triglyceride hydrolysis but also serve as
a ligand/bridging factor for receptor-mediated lipoprotein
uptake . Besides, lipoproteins derived from plasma have
been proved to be the crucial upstream source of fatty acids
within Bruch?s membrane and supply an energy source to
the retina [
] as well as perform significant roles in the
transportation of vitamin C, vitamin E, lutein, and
zeaxanthin for use by photoreceptors [
dysfunction of CETP, LIPC, LPL, ABCA1, and ABCG1 may
cause accumulation of oxidized lipids in the retina, and the
unreasonable products could induce inflammation and
vascular anomaly, which play a crucial role in the
development of PCV and AMD via lipid metabolism [
In the studies (including 3 in Chinese [
33, 35, 36
] and 1
in Japanese [
]), we found that CETP rs3764261 was to be
associated with PCV in Asian population with an odds ratio
of 1.46 (95% CI: 1.28?1.665, P 0, I2 0%) for the T allele.
Apart from CETP rs3764261, we also found that CETP
Heterogeneity chi-squared = 0.16 (d.f. = 1) p = 0.687
I-squared (variation in OR attributable to heterogeneity) = 0.0%
Test of OR = 1 : z = 1.01 p = 0.312
rs2303790 was associated with PCV in Asian population
] (G allele; OR 1.57, 95% CI: 1.258?1.96, P < 0.01,
I2 0). ?erefore, CETP rs3764261/rs2303790 provided an
increased risk for PCV in Asian population. ?rough the
analysis of the studies in which both PCV and AMD were
assessed for associations with CETP, we found CETP
rs2303790 showed no signi cant di?erence between PCV
and AMD. However, as for CETP rs3764261, two studies
dedicated that CETP rs3764261 was signi cantly associated
with an increased risk for PCV, but no association was found
with AMD(T allele; OR 1.301, 95% CI: 1.033?1.638,
P 0.025, I2 0%) [
], but one study showed that
CETP rs3764261 is a susceptibility gene for PCV and AMD
]. According to the article of GWAS and meta-analysis
published by Cheng et al., the minor allele at CETP
rs3764261 variant was proved to be a risk factor to the
development of AMD in Asian population [
several recent studies indicated that CETP rs3764261 was
related to a decreased risk of AMD in Chinese population
and Lithuanian population [
]. ?erefore, it is still
disputed whether CETP rs3764261 has di?erent e?ects in
PCV and AMD, and we need further studies in which both
PCV and AMD are assessed for associations with CETP to
con rm it.
From the studies [
], for ABCG1 rs57137919, the
frequency of the A allele in PCV patients was signi cantly
higher than in controls (OR 1.168, 95% CI: 1.016?1.343,
P 0.029, I2 61.5%). Interestingly, we found the result had
the heterogeneity. ?rough quality assessment and
sensitivity analysis, we found the heterogeneity derived from the
data of Shantou population. After reading the related
articles, we found all the studies used TaqMan genotyping
assays, as well as the same inclusion criteria and exclusion
criteria. ?erefore, we speculate that there may be racial
di?erences between Shantou population and others, but we
need further studies to prove the view and nd the causes of
heterogeneity. Also, we found the signi cant di?erence
between PCV and AMD in ABCG1 rs57137919 (G allele;
OR 1.208, 95% CI: 1.035?1.411, P 0.017, I2 0%). In one
of the studies, Li et al. studied the relevance of ABCG1
rs57137919 to PCV and AMD in Hong Kong, Shantou, and
Osaka study subjects, and the results showed that the as
sociation of ABCG1 rs57137919 with PCV was signi cant in
the Hong Kong cohort, but not in the Shantou or the Osaka
cohort. Also, they indicated that the association of ABCG1
rs57137919 with AMD was not signi cant in the Hong Kong,
Shantou, and Osaka cohorts. In another study, Liu et al.
provided putative evidence of a role of ABCG1 rs57137919 in
the vascularized complication of PCV. Because there were
only two studies about relevance of ABCG1 rs57137919 to
PCV and AMD, we need further replication studies in other ethnic populations to con rm the role of ABCG1 in PCV and AMD.
From our meta-analysis, we found other 4 SNPs (LIPC
rs10468017/rs493258, LPL rs12678919, and ABCA1 rs1883025)
were not statistically signi cant in PCV and AMD. Besides, the
associations of eleven SNPs in CETP/LIPC/ABCA1/ABCG1
were reported in only 1 study [
] (details can be seen in
Table S5). Among these SNPs, Zhang et al. discovered that the
rs5882 variant in CETP was signi cantly associated with PCV
(G allele; P 0.73E ? 04), but not with AMD (G allele;
P 0.297), and suggested the need to nd biological clues
about the di?erent underlying HDL pathways by separating
PCV from AMD so as to explore the pathogenesis of PCV and AMD .
Another recent study reported that LIPC rs1532085
conferred an increased risk for PCV (A allele; P 0.0094), but
not AMD (A allele; P 0.0938). Also, this study found
hyperlipidemia is a risk factor for PCV [
]. Recently, Li et al.
have newly identi ed ABCG1 rs225396 to be associated with
PCV (T allele; P 0.026) and AMD (T allele; P 0.048) in
Chinese and Japanese subjects, which pointed out ABCG1 as
a new susceptibility gene for PCV and AMD [
]. In 2017,
Qiao et al. reported that the strongest PCV-associated SNP,
CETP rs183130 (T allele; P 3.07E ? 07), was in high LD with
the currently studied SNP rs3764261 in Europeans, and similar
association patterns were shown in AMD at CETP rs183130
(T allele; P 4.31E ? 05). Also, they found that the most
significant association signals recognized in Europeans were at
rs5817082, rs1864163, and rs17231506 in CETP, but only
rs17232506 showed significant association with PCV and
]. However, all the results above were reported in
only 1 study, and they were challenged by pretty small sample
sizes, so we need more researches with independent cohorts to
verify these association findings.
In conclusion, our systematic review and meta-analysis
has provided an overview of the association profiles of genes
in the HDLMP in PCV for the first time and assessed the
genetic difference in the HDLMP between PCV and AMD.
-e results suggest that CETP (rs3764261/rs2303790) and
ABCG1 (rs57137919) are the major susceptibility genes for
PCV in the Asian population, and ABCG1 (rs57137919) has
different effects in PCV and AMD in the Asian population.
However, due to the small pooled sample size for PCV and
AMD, further studies of these genes in larger samples are
warranted to confirm the association of gene variations in the
HDLMP with PCV in other populations such as Caucasian
and Australian. Moreover, further studies should focus on the
genotype-phenotype correlations and the relevance of
genotype to therapy in PCV, which may provide us the clues
about the pathogenesis of PCV.
Conflicts of Interest
-e authors declare that there are no conflicts of interest
regarding the publication of this paper.
Table S1: the search strategy applied in all databases. Table S2:
lists of included/excluded studies with reasons. Table S3:
Hardy?Weinberg equilibrium of polymorphisms in
control subjects. Table S4: quality assessment of each study
based on the Newcastle?Ottawa Scale. Table S5: the number
of studies for CETP/LIPC/LPL/ABCA1/ABCG1
polymorphisms in PCV. Figure S1: funnel plot of 7 SNPs in
PCV in the allelic model. Figure S2: funnel plot of 7 SNPs
compared between PCV and AMD in the allelic model.
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