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Association between the ABCA1 (R219K) polymorphism and lipid profiles: a meta-analysis

ABSTRACT: Conflicting evidence was found about the relationship between lipid profiles and R219K polymorphism in adenosine triphosphate-binding cassette exporter A1 (ABCA1) gene. In this study, four meta-analyses were conducted to assess the effect of R219K on lipid levels, including high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol, total cholesterol, and triglycerides (TG). A total of 125 samples of 87 studies (about 60,262 subjects) were included. The effect of each study was expressed using the standard mean difference (SMD) and 95% confidence interval (95% CI) and pooled by meta-analysis in the random-effects model. Subgroup and meta-regression analyses were conducted to explore potential heterogeneity sources. The overall pooled effect showed the following results. (1) The R219K was significantly associated with HDLC level (SMD = − 0.25 mmol/L, 95%CI − 0.32 to − 0.18, z = − 6.96, P < 0.01, recessive genetic model). People with different genotypes had significantly different HDLC levels under the recessive, codominant and dominant genetic models (all Ps < 0.01). (2) A weak and indeterminate relationship between R219K and TG level was observed (SMD = 0.18 mmol/L, 95%CI 0.06–0.30, z = 3.01, P < 0.01, recessive genetic model). These findings suggested that R219K was associated with HDLC and TG levels, which might implicate a promising clinical application for lipid-related disorders, though the influences of race, health status, BMI, and other heterogeneity sources should be considered when interpreting current findings. The protocol was registered at PROSPERO (registration number: CRD42021231178).

SUBMITTER: Shi Z

PROVIDER: S-EPMC8571387 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Accumulated evidence suggests that adverse lipid changes are risk factors for type 2 diabetes mellitus (T2DM) and neurodegenerative disorders. The ATP-binding cassette A1 transporter (ABCA1) gene contributes to both lipid processing and amyloid-? formation and thus shows promise as a biological target in the pathology of mild cognitive impairment (MCI) in T2DM. Objective: This study aimed to investigate the interactions among lipids, ABCA1 R219K polymorphism, and cognitive function in T2DM. Methods: Clinical parameters, including lipids, were measured. The testing scores of different cognitive domains were recorded, and the ABCA1 R219K polymorphisms were analyzed. Results: A total of 226 patients, including 124 MCI patients and 102 controls, were enrolled in this study. T2DM patients with MCI showed lower cognitive functions, serum high-density lipoprotein (HDL-c), and apolipoprotein A1 (apoA-I) levels; and higher total cholesterol level than the controls. Serum HDL-c (P = 0.001) and apoA-I (P = 0.016) were positively associated with the MoCA score in MCI patients. Further stratification analyses revealed that the subjects with higher HDL-c concentration showed better attention and memory for verbal, visual, and logical functions than the group with lower HDL-c concentration (P < 0.05). No significant differences were observed among the distributions of ABCA1 R219K variants between MCI patients and controls; however, the KK genotype carriers presented higher apoA-I levels than those with RR genotype in MCI individuals. Conclusion: This study does not support the association between R219K polymorphism and T2DM-related MCI. However, our data suggested that the serum HDL-c level might positively influence cognition, especially memory function, in T2DM patients. Further studies are needed to determine the interaction between lipids and ABCA1 genotype and its effect on cognition in T2DM patients. Trial registration: Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis ChiCTR-OCC-15006060; http://www.chictr.org.cn/showproj.aspx?proj=10536.

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Association between the ABCA1 (R219K) polymorphism and lipid profiles: a meta-analysis

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