The SNPs rs429358 and rs7412 of APOE gene are association with cerebral infarction but not SNPs rs2306283 and rs4149056 of SLCO1B1 gene in southern Chinese Hakka population

Abstract Background: Apolipoprotein E (ApoE) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) are involved in regulating lipid metabolism. However, the relationship between genetic polymorphisms of APOE and SLCO1B1 and cerebral infarction (CI) remains unclear. Methods: A total of 938 CI patients and 1,028 control participants were included in the study. The single nucleotide polymorphisms (SNPs) rs429358 and rs7412 of the APOE gene and SNPs rs2306283 and rs4149056 of the SLCO1B1 gene were analysed by fluorescence polymerase chain reaction (PCR). Results: The genotype ɛ3/ɛ3 was the most common APOE genotype, with ɛ3 being the allele with the highest frequency, followed by ɛ4 and ɛ2. Statistically significant differences of genotype ɛ2/ɛ2 ( c 2 =3.866, P =0.049), ɛ2/ɛ3 (c 2 =20.030, P <0.001), ɛ3/ɛ4 (c 2 =16.960, P <0.001), and ɛ4/ɛ4 (c 2 =4.786, P =0.029) between CI patients and controls were detected. The SLCO1B1 genotype *1b/*1b and haplotype *1b showed the highest frequency in the study sample. There was no statistically significant difference in the frequencies of SLCO1B1 genotypes and haplotypes among CI patients comparing with controls. Moreover, ε4 carriers had significantly higher low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (Apo-B) and lower apolipoprotein A1 (Apo-A1)/Apo-B levels than ε2 and ε3 carriers, but ε2 carriers showed lower LDL-C and Apo-B and higher Apo-A1/Apo-B than ε3 and ε4 carriers. Further, logistic regression analysis revealed that high LDL-C, high ApoB, smoking, hypertension and the ε4 allele were risks for the presence of CI. Conclusions: This study indicated that the APOE SNPs rs429358 and rs7412 may be associated with susceptibility to cerebral infarction in southern Chinese Hakka population.

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The SNPs rs429358 and rs7412 of APOE gene are association with cerebral infarction but not SNPs rs2306283 and rs4149056 of SLCO1B1 gene in southern Chinese Hakka population

10.21203/rs.3.rs-37980/v3 ◽

2020 ◽

Author(s):

Heming Wu ◽

Qingyan Huang ◽

Zhikang Yu ◽

Hailing Wu ◽

Zhixiong Zhong

Keyword(s):

Cerebral Infarction ◽

Organic Anion ◽

Organic Anion Transporter ◽

Apolipoprotein A1 ◽

Nucleotide Polymorphisms ◽

Apo B ◽

Southern Chinese ◽

Anion Transporter ◽

Transporter Family ◽

Significant Difference

Abstract Background: Apolipoprotein E (ApoE) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) regulate lipid metabolism. However, the relationship between genetic polymorphisms of APOE and SLCO1B1 and cerebral infarction (CI) remains unclear.Methods: A total of 938 CI patients and 1,028 control participants were included in the study. The rs429358 and rs7412 single nucleotide polymorphisms (SNPs) in the APOE gene and rs2306283 and rs4149056 SNPs in the SLCO1B1 gene were analyzed by fluorescence polymerase chain reaction (PCR).Results: The genotype ɛ3/ɛ3 was the most common APOE genotype, with ɛ3 being the allele with the highest frequency, followed by ɛ4 and ɛ2. Statistically significant differences of genotype ɛ2/ɛ2 (c2=3.866, P=0.049), ɛ2/ɛ3 (c2=20.030, P<0.001), ɛ3/ɛ4 (c2=16.960, P<0.001), and ɛ4/ɛ4 (c2=4.786, P=0.029) between CI patients and controls were detected. The SLCO1B1 genotype *1b/*1b and haplotype *1b showed the highest frequency in the study sample. There was no statistically significant difference in the frequencies of SLCO1B1 genotypes and haplotypes among CI patients comparing with controls. Moreover, ε4 carriers had significantly higher low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (Apo-B) and lower apolipoprotein A1 (Apo-A1)/Apo-B levels than ε2 and ε3 carriers, but ε2 carriers showed lower LDL-C and Apo-B and higher Apo-A1/Apo-B than ε3 and ε4 carriers. Further, logistic regression analysis revealed that high LDL-C, high ApoB, smoking, hypertension and the ε4 allele were risks for the presence of CI.Conclusions: This study indicated that the APOE SNPs rs429358 and rs7412 may be associated with susceptibility to cerebral infarction in southern Chinese Hakka population.

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The SNPs rs429358 and rs7412 of APOE gene are association with cerebral infarction but not SNPs rs2306283 and rs4149056 of SLCO1B1 gene in southern Chinese Hakka population

10.21203/rs.3.rs-37980/v1 ◽

2020 ◽

Author(s):

Heming Wu ◽

Qingyan Huang ◽

Zhikang Yu ◽

Hailing Wu ◽

Zhixiong Zhong

Keyword(s):

Cerebral Infarction ◽

Organic Anion ◽

Organic Anion Transporter ◽

Nucleotide Polymorphisms ◽

Apo B ◽

Southern Chinese ◽

Anion Transporter ◽

Transporter Family ◽

Significant Difference ◽

Pcr Method

Abstract Background: Apolipoprotein E (ApoE) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) are involved in regulating lipid metabolism. However, the relation between genetic polymorphisms of APOE and SLCO1B1 and cerebral infarction (CI) remains unclear.Methods: A total of 945 CI patients and 1,028 control participants were included in the study. The single nucleotide polymorphisms (SNPs) rs429358, rs7412 of APOE gene and SNPs rs2306283, rs4149056 of SLCO1B1 gene were analyzed by fluorescence polymerase chain reaction (PCR) method.Results: The genotype ɛ3/ɛ3 is the most common genotype of APOE gene, in which ɛ3 is the allele with greatest frequency, followed by ɛ4 and ɛ2. There were statistically significant differences of genotype ɛ2/ɛ2 (c2=4.718, P=0.030), ɛ2/ɛ3 (c2=18.076, P<0.001), ɛ3/ɛ4 (c2=18.714, P<0.001), ɛ4/ɛ4 (c2=4.710, P=0.046) in CI patients comparing with controls. The SLCO1B1 genotype *1b/*1b and haplotype *1b have greatest frequency in the study sample. There was no statistically significant difference in frequencies of SLCO1B1 genotypes and haplotypes in CI patients comparing with controls. Moreover, the ε4 carriers had significantly higher LDL-C, Apo-B, and lower Apo-A1/Apo-B than the other groups, while the ε2 carriers showed the opposite results in the CI group and controls. Logistic regression analysis indicated that participants with ε4 allele had a significantly higher risk of CI in males (OR 3.508, 95% CI 2.186-5.629, P<0.001) and females (OR 2.723, 95% CI 1.428-5.194, P=0.002).Conclusions: The study indicated that the SNPs rs429358 and rs7412 of APOE may be associated with susceptibility to cerebral infarction, in southern Chinese Hakka population.

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Frequencies of Single-Nucleotide Polymorphisms and Haplotypes of the SLCO1B1 Gene in Selected Populations of the Western Balkans

Balkan Journal of Medical Genetics ◽

10.1515/bjmg-2015-0001 ◽

2015 ◽

Vol 18 (1) ◽

pp. 5-22 ◽

Cited By ~ 3

Author(s):

A. Daka Grapci ◽

A. J. Dimovski ◽

A. Kapedanovska ◽

M. Vavlukis ◽

A. Eftimov ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Ethnic Groups ◽

Organic Anion ◽

Nucleotide Polymorphisms ◽

Western Balkans ◽

Single Nucleotide ◽

Anion Transporter ◽

Significant Difference ◽

Variant Alleles ◽

Slco1b1 Gene

Abstract As a membrane influx transporter, organic anion- transporting polypeptide 1B1 (OATP1B1) regulates the cellular uptake of a number of endogenous compounds and drugs. The aim of this study was to characterize the diversity of the solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene encoding this transporter in two ethnic groups populating the Western Balkans. The distribution of SCLO1B1 alleles was determined at seven variant sites (c.388A>G, c.521T>C, c.571T>C, c.597C>T, c.1086C>T, c.1463G>C and c.*439T>G) in 266 Macedonians and 94 Albanians using the TaqMan allelic discrimination assay. No significant difference in the frequencies of the single nucleotide polymorphisms (SNPs) was observed between these populations. The frequency of the c.521T>C SNP was the lowest (<13.7 and 12.2%, respectively), while the frequencies of all other SNP alleles were above 40.0%. Variant alleles of c.1463G>C and c.1086 C>T SNPs were not identified in either ethnic group. The haplotype analysis revealed 20 and 21 different haplotypes in the Macedonian and Albanian population, respectively. The most common haplotype in both ethnic groups, *1J/*1K/*1L, had a frequency of 39.0% and 26.6%, respectively. In both populations, the variant alleles of the functionally significant c.521T>C and c.388A>G SNPs existed in one major haplotype (*15/*16/*17), with a frequency of 8.6 and 2.4% in the Macedonian and Albanian subjects, respectively. In conclusion, sequence variations of the SLCO1B1 gene in the studied populations occur at high frequencies, which are similar to that of the Caucasian population. Further studies are needed to evaluate the clinical significance of these SNPs and/ or the major SLCO1B1 haplotypes they form for a large number of substrates and for susceptibility to certain diseases.

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The SNPs rs429358 and rs7412 of APOE gene are association with cerebral infarction but not SNPs rs2306283 and rs4149056 of SLCO1B1 gene in southern Chinese Hakka population

Lipids in Health and Disease ◽

10.1186/s12944-020-01379-4 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Heming Wu ◽

Qingyan Huang ◽

Zhikang Yu ◽

Hailing Wu ◽

Zhixiong Zhong

Keyword(s):

Cerebral Infarction ◽

Apoe Gene ◽

Southern Chinese ◽

Slco1b1 Gene

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A Systematic Review and Meta-Analysis of Therapeutic Efficacy and Safety of Alirocumab and Evolocumab on Familial Hypercholesterolemia

BioMed Research International ◽

10.1155/2021/8032978 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Xiaoyue Ge ◽

Tiantian Zhu ◽

Hao Zeng ◽

Xin Yu ◽

Juan Li ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Familial Hypercholesterolemia ◽

Meta Analysis ◽

Density Lipoprotein ◽

Apolipoprotein A1 ◽

Cochrane Library ◽

Efficacy And Safety ◽

Apo B ◽

Significant Difference

Objectives. The aim of this study was to provide the first study to systematically analyze the efficacy and safety of PCSK9-mAbs in the treatment of familial hypercholesterolemia (FH). Methods. A computer was used to search the electronic Cochrane Library, PubMed/MEDLINE, and Embase databases for clinical trials using the following search terms: “AMG 145”, “evolocumab”, “SAR236553/REGN727”, “alirocumab”, “RG7652”, “LY3015014”, “RN316/bococizumab”, “PCSK9”, and “familial hypercholesterolemia” up to November 2020. Study quality was assessed with the Cochrane Collaboration’s tool, and publication bias was evaluated by a contour-enhanced funnel plot and the Harbord modification of the Egger test. After obtaining the data, a meta-analysis was performed using R software, version 4.0.3. Results. A meta-analysis was performed on 7 clinical trials (926 total patients). The results showed that PCSK9-mAbs reduced the LDL-C level by the greatest margin, WMD −49.14%, 95% CI: −55.81 to −42.47%, on FH versus control groups. PCSK9-mAbs also significantly reduced lipoprotein (a) (Lp (a)), total cholesterol (TC), triglycerides (TG), apolipoprotein-B (Apo-B), and non-high-density lipoprotein cholesterol (non-HDL-C) levels and increased HDL-C and apolipoprotein-A1 (Apo-A1) levels of beneficial lipoproteins. Moreover, no significant difference was found between PCSK9-mAbs treatment and placebo in common adverse events, serious events, and laboratory adverse events. Conclusion. PCSK9-mAbs significantly decreased LDL-C and other lipid levels with satisfactory safety and tolerability in FH treatment.

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Mechanisms of glutathione-conjugate efflux from the brain into blood: Involvement of multiple transporters in the course

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x18808399 ◽

2018 ◽

Vol 40 (1) ◽

pp. 116-125 ◽

Cited By ~ 1

Author(s):

Toshimitsu Okamura ◽

Maki Okada ◽

Tatsuya Kikuchi ◽

Hidekatsu Wakizaka ◽

Ming-Rong Zhang

Keyword(s):

Organic Anion ◽

Organic Anion Transporter ◽

Cancer Resistance ◽

Efflux Rate ◽

Glutathione Conjugate ◽

Glutathione Conjugates ◽

Anion Transporter ◽

Significant Difference ◽

The Brain

Accumulation of detrimental glutathione-conjugated metabolites in the brain potentially causes neurological disorders, and must therefore be exported from the brain. However, in vivo mechanisms of glutathione-conjugates efflux from the brain remain unknown. We investigated the involvement of transporters in glutathione-conjugates efflux using 6-bromo-7-[11C]methylpurine ([11C]1), which enters the brain and is converted into its glutathione conjugate, S-(7-[11C]methylpurin-6-yl)glutathione ([11C]2). In mice of control and knockout of P-glycoprotein/breast cancer resistance protein and multidrug resistance-associated protein 2 ([ Mrp2] −/−), [11C]2 formed in the brain was rapidly cleared, with no significant difference in efflux rate. In contrast, [11C]2 formed in the brain of Mrp1 −/− mice was slowly cleared, whereas [11C]2 microinjected into the brain of control and Mrp1 −/− mice was 75% cleared within 60 min, with no significant difference in efflux rate. These suggest that Mrp1 contributes to [11C]2 efflux across cell membranes, but not BBB. Efflux rate of [11C]2 formed in the brain was significantly lower in Mrp4 −/− and organic anion transporter 3 ( Oat3) −/− mice compared with control mice. In conclusion, Mrp1, Oat3, and Mrp4 mediate [11C]2 efflux from the brain. Mrp1 may contribute to [11C]2 efflux from brain parenchymal cells, while extracellular [11C]2 is likely cleared across the BBB, partly by Oat3 and Mrp4.

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SLCO1B1 Gene Polymorphisms (rs2306283 and rs4149056) and Statin-Induced Myopathy in Jordanian Diabetics

Current Clinical Pharmacology ◽

10.2174/1574884715666200827105612 ◽

2020 ◽

Vol 15 ◽

Author(s):

Zaineh M. Shahrure ◽

Yacoub M. Irshaid ◽

Khader N. Mustafa ◽

Mousa A. Abujbara ◽

Mohammad Al Shhab ◽

...

Keyword(s):

Genetic Polymorphism ◽

Intracellular Transport ◽

Organic Anion ◽

Venous Blood ◽

Minor Allele ◽

Organic Anion Transporter ◽

Amplification Refractory Mutation System ◽

Anion Transporter ◽

Informed Consent Form ◽

Slco1b1 Gene

Background: The use of statins to lower high serum cholesterol levels may be associated with a number of adverse reactions, including severe myopathy. The solute carrier organic anion transporter 1B1 (SLCO1B1) gene, which encodes the organic anion-transporting polypeptide OATP1B1 is related to the intracellular transport of statins. The aim of this research is to study the association of rs2306283 and rs4149056 genetic polymorphism of SLCO1B1 gene with the development of statin-induced myopathy in Jordanian diabetics receiving statins. Methods: We included 413 patients attending the Diabetes Clinics of the National Center for Diabetes, Endocrinology and Genetics), Amman, Jordan. The study was approved by the Institutional Review Board of NCDEG. Myopathy was defined as elevation of creatine kinase more than 3 times the upper limit of normal. Every subject signed an informed consent form and donated 3-5 mL of venous blood. Genome DNA was extracted from lymphocytes of peripheral blood. Genotypes were identified using Tetra Amplification Refractory Mutation System of SLCO1B1. Results: The minor allele frequencies of rs2306283 [G] and rs4149056 [C] were 0.38 and 0.23, respectively. The two SNPs followed the Hardy-Weinberg equilibrium. The development of SIM was significantly associated with the homozygous and heterozygous minor allele genotype of rs4149056 (CC and CT), and the homozygous wild type allele genotype of rs2306283 (AA). There was no linkage disequilibrium between the two SNPs the studied subgroups. Conclusions: Genetic polymorphism in the SLCO1B1 Gene is a risk factor for the development of SIM in Jordanian patients.

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