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Apolipoprotein A1 -75 G/A and +83 C/T polymorphisms and renal cancer risk.

ABSTRACT: Apolipoprotein A1 (ApoA1) is the major apoprotein constituent of high-density lipoprotein that can play important roles in tumor invasion and metastasis. The objective of the present study was to evaluate the association of two genetic variants (-75 G/A and +83 C/T) of APOA1 with predisposition to renal cancer.A total of 432 subjects, including 216 pathologically-proven renal cancer cases and 216 age- and gender-matched healthy controls, were recruited into this hospital-based case-control study. Genotyping of the APOA1 was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with gel electrophoresis, and then confirmed by direct sequencing.Patients with renal cancer had a significantly higher frequency of APOA1 -75 AA genotype [odds ratio (OR)?=?2.10, 95% confidence interval (CI)?=?1.18, 3.75; P?=?0.01] and APOA1 -75 A allele (OR =1.40, 95% CI?=?1.05, 1.87; P?=?0.02) than controls. When stratifying by the distant metastasis status, patients with distant metastasis had a significantly higher frequency of APOA1 -75 AA genotype genotype (OR =2.20, 95% CI?=?1.04, 4.68; P?=?0.04).This study is, to our knowledge, the first to examine prospectively an increased risk role of APOA1 -75 AA genotype and APOA1 -75 A allele in renal cancer susceptibility.

SUBMITTER: Liu Z

PROVIDER: S-EPMC4634729 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Apolipoprotein A1 -75 G/A and +83 C/T polymorphisms and renal cancer risk.

Liu ZhiHong Z Xiao YingMing Y Tang LiangYou L Jiang Liang L Wang YuJie Y Zhang RuoChen R Wei Qiang Q Lu YiPing Y

Lipids in health and disease 20151104

<h4>Background</h4>Apolipoprotein A1 (ApoA1) is the major apoprotein constituent of high-density lipoprotein that can play important roles in tumor invasion and metastasis. The objective of the present study was to evaluate the association of two genetic variants (-75 G/A and +83 C/T) of APOA1 with predisposition to renal cancer.<h4>Methods</h4>A total of 432 subjects, including 216 pathologically-proven renal cancer cases and 216 age- and gender-matched healthy controls, were recruited into thi ...[more]

PMID: 26537097

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Project description:BackgroundCardiovascular disease is a leading cause of mortality in patients with juvenile-onset systemic lupus erythematosus (JSLE). Traditional factors for cardiovascular risk (CVR) prediction are less robust in younger patients. More reliable CVR biomarkers are needed for JSLE patient stratification and to identify therapeutic approaches to reduce cardiovascular morbidity and mortality in JSLE.MethodsSerum metabolomic analysis (including >200 lipoprotein measures) was performed on a discovery (n=31, median age 19) and validation (n=31, median age 19) cohort of JSLE patients. Data was analysed using cluster, receiver operating characteristic analysis and logistic regression. RNA-sequencing assessed gene expression in matched patient samples.FindingsHierarchical clustering of lipoprotein measures identified and validated two unique JSLE groups. Group-1 had an atherogenic and Group-2 had an atheroprotective lipoprotien profile. Apolipoprotein(Apo)B:ApoA1 distinguished the two groups with high specificity (96.2%) and sensitivity (96.7%). JSLE patients with high ApoB:ApoA1 ratio had increased CD8+ T-cell frequencies and a CD8+ T-cell transcriptomic profile enriched in genes associated with atherogenic processes including interferon signaling. These metabolic and immune signatures overlapped statistically significantly with lipid biomarkers associated with sub-clinical atherosclerosis in adult SLE patients and with genes overexpressed in T-cells from human atherosclerotic plaque respectively. Finally, baseline ApoB:ApoA1 ratio correlated positively with SLE disease activity index (r=0.43, p=0.0009) and negatively with Lupus Low Disease Activity State (r=-0.43, p=0.0009) over 5-year follow-up.InterpretationMulti-omic analysis identified high ApoB:ApoA1 as a potential biomarker of increased cardiometabolic risk and worse clinical outcomes in JSLE. ApoB:ApoA1 could help identify patients that require increased disease monitoring, lipid modification or lifestyle changes.FundingLupus UK, The Rosetrees Trust, British Heart Foundation, UCL & Birkbeck MRC Doctoral Training Programme and Versus Arthritis.

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Apolipoprotein A1 -75 G/A and +83 C/T polymorphisms and renal cancer risk.

Publications

Apolipoprotein A1 -75 G/A and +83 C/T polymorphisms and renal cancer risk.

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