Genetic association study of APOA1/C3/A4/A5 gene cluster and haplotypes on triglyceride and HDL cholesterol in a community-based population

Chien, Kuo–Liong; Chen, Ming-Fong; Hsu, Hsiu-Ching; Su, Ta‐Chen; Chang, Wei‐Tien; Lee, Chi-Ming; Lee, Yuan‐Teh

doi:10.1016/j.cca.2007.10.006

Cited by 31 publications

(27 citation statements)

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“…(32). There are numerous reports on the association of genetic variants of APOA5 with low HDL-C levels, such as rs662799, rs651821, and rs2075291 in Japanese populations (33) and Chinese populations (34). The SNP of rs3135506 is significantly associated with blood HDL-C levels in northern American (35) and Austrian Caucasian subjects (36).…”

Section: Discussionmentioning

confidence: 99%

Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations

Dollé

Imholz

et al. 2008

Journal of Lipid Research

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The known genetic variants determining plasma HDL cholesterol (HDL-C) levels explain only part of its variation. Three hundred eighty-four single nucleotide polymorphisms (SNPs) across 251 genes based on pathways potentially relevant to HDL-C metabolism were selected and genotyped in 3,575 subjects from the Doetinchem cohort, which was examined thrice over 11 years. Three hundred fifty-three SNPs in 239 genes passed the quality-control criteria. Seven SNPs [rs1800777 and rs5882 in cholesteryl ester transfer protein (CETP); rs3208305, rs328, and rs268 in LPL; rs1800588 in LIPC; rs2229741 in NRIP1] were associated with plasma HDL-C levels with false discovery rate (FDR) adjusted q values (FDR_q) , 0.05. Five other SNPs (rs17585739 in SC4MOL, rs11066322 in PTPN11, rs4961 in ADD1, rs6060717 near SCAND1, and rs3213451 in MBTPS2 in women) were associated with plasma HDL-C levels with FDR_q between 0.05 and 0.2. Two less well replicated associations (rs3135506 in APOA5 and rs1800961 in HNF4A) known from the literature were also observed, but their significance disappeared after adjustment for multiple testing (P 5 0.008, FDR_q 5 0.221 for rs3135506; P 5 0.018, FDR_q 5 0.338 for rs1800961, respectively). In addition to replication of previous results for candidate genes (CETP, LPL, LIPC, HNF4A, and APOA5), we found interesting new candidate SNPs (rs2229741 in NRIP1, rs3213451 in MBTPS2, rs17585739 in SC4MOL, rs11066322 in PTPN11, rs4961 in ADD1, and rs6060717 near SCAND1) for plasma HDL-C levels that should be evaluated further. Numerous clinical and epidemiological studies have demonstrated an inverse and independent association between plasma concentrations of HDL cholesterol (HDL-C) and the risk of coronary heart disease (1). The most popular mechanistic explanation has been that HDL functions in reverse cholesterol transport, removing cholesterol from peripheral tissues and delivering it to the liver for biliary excretion and to steroidogenic organs for steroid hormones synthesis (2). Although efflux of cholesterol from macrophages represents only a tiny fraction of overall cellular cholesterol efflux, it is in fact, the most important with regard to antiatherogenic effects (3). More recently, a variety of other functions of HDL have been described, primarily based on in vitro assays, including anti-inflammatory, antioxidant, antithrombotic, and nitric oxide-inducing mechanisms that could also contribute to its antiatherogenic effects (4, 5).Current evidence suggests that blood lipids are complex phenotypes, influenced by environmental and genetic factors. It has been well established that body weight (6), current smoking habits (7), exercise (8), alcohol use (9), and dietary fat intake (10) influence plasma HDL-C levels. Several twin and family studies indicate that heritability estimates for blood levels of HDL-C range from 24% to 83%, with most studies in the 40% to 60% range (11). Mutations in genes including ABC transporter A1 (ABCA1), apolipoprotein A1, and lecithin cholesterol transferase (LCAT) are ...

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Section: Discussionmentioning

confidence: 99%

Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations

Dollé

Imholz

et al. 2008

Journal of Lipid Research

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“…Apolipoproteins are closely involved in lipid metabolism. APOA1/C3/A4/A5 gene cluster, located in 11q23, has been associated with familial combined hyperlipidemia [4,5] and with lipid plasma levels [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein A1 gene polymorphisms as risk factors for hypertension and obesity

et al. 2009

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Several polymorphisms in apolipoprotein A1 (APOA1) gene have been associated with metabolic diseases. Increased transcription efficiency was observed in -75A allele carriers compared to -75G allele homozygotes. +83C allele was associated with higher body mass index and waist-to-hip ratio in type II diabetes subjects. -75G/A and +83C/T polymorphisms were analyzed by RFLP-PCR in 334 individuals from a Brazilian elderly cohort. APOA1 polymorphisms were associated with age-related morbidities, as well as with triglycerides, total cholesterol, HDL, VLDL, LDL, creatinine, urea, albumin, glycated hemoglobin and fasting glucose serum levels. Allele frequencies were 0.102 and 0.21, respectively, for -75A and +83T. -75G allele showed significant association with hypertension (P = 0.001). An association between +83C allele and obesity was observed (P = 0.040) and this allele also showed an association with hypertension in the presence of cardiovascular disease (P = 0.047). Moreover, +83T allele was associated with lower glycated hemoglobin values (P = 0.026). To our knowledge, there is no data associating this polymorphism with glycated hemoglobin. Furthermore, individuals carrying AT haplotype have lower risk for developing hypertension (P = 0.0002), while GT haplotype carriers present decreased risk to develop obesity comparing to GC haplotype (P = 0.025). APOA1 polymorphisms analysis may be a useful tool to identify risk factors for subjects and families and clarify the physiopathological role of these polymorphisms in age-related diseases, such as hypertension and obesity.

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“…We selected polymorphisms of the genes CETP, APOA1 and SCARB1 for a combined evaluation. Although some authors detected isolated effects of these genes on HDL-C levels, several other studies found that the influence of these genes is too weak to be detected when they are evaluated separately 13,26,31,32 .…”

Section: Discussionmentioning

confidence: 99%

Influência de combinações genéticas nos níveis de HDL-c em uma população do sul do Brasil

Andrade¹,

Fiegenbaum²,

Almeida³

et al. 2010

Arq. Bras. Cardiol.

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Genetic association study of APOA1/C3/A4/A5 gene cluster and haplotypes on triglyceride and HDL cholesterol in a community-based population

Cited by 31 publications

References 50 publications

Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations

Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations

Apolipoprotein A1 gene polymorphisms as risk factors for hypertension and obesity

Influência de combinações genéticas nos níveis de HDL-c em uma população do sul do Brasil

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