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 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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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/v2 ◽

2020 ◽

Author(s):

Heming Wu ◽

Qingyan Huang ◽

Zhikang Yu ◽

Hailing Wu ◽

Zhixiong Zhong

Keyword(s):

Cerebral Infarction ◽

Organic Anion ◽

Apoe Genotype ◽

Apoe Gene ◽

Apolipoprotein A1 ◽

Apo B ◽

Southern Chinese ◽

Anion Transporter ◽

Significant Difference ◽

Slco1b1 Gene

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 organic anion transporter family: from physiology to ontogeny and the clinic

AJP Renal Physiology ◽

10.1152/ajprenal.2001.281.2.f197 ◽

2001 ◽

Vol 281 (2) ◽

pp. F197-F205 ◽

Cited By ~ 100

Author(s):

Douglas H. Sweet ◽

Kevin T. Bush ◽

Sanjay K. Nigam

Keyword(s):

Kidney Development ◽

Organic Anion ◽

Organic Anion Transporter ◽

New Drugs ◽

Spatiotemporal Pattern ◽

Nucleotide Polymorphisms ◽

Anion Transporter ◽

Transporter Family ◽

Computer Based ◽

Anionic Drugs

The organic anion transporter (OAT) family handles a wide variety of clinically important compounds (antibiotics, nonsteriodal anti-inflammatory drugs, etc.) and toxins. However, little is known about their appearance during development despite documented differences in the handling of anionic drugs among neonates, children, and adults. A similar spatiotemporal pattern of mRNA expression of the OATs (OAT1–4) during kidney development suggests that OAT genes may be useful in understanding the mechanisms of proximal tubule maturation. Moreover, OAT expression in unexpected extrarenal sites (e.g., spinal cord, bone, skin) has also been detected during development, possibly indicating a role for these transporters in the formation or preservation of extrarenal tissues. The cloning of these transporters also paves the way for computer-based modeling of drug-transporter interactions at the molecular level, potentially aiding in the design and assessment of new drugs. Additionally, increased understanding of single nucleotide polymorphisms in OATs and other transporters may eventually allow the use of a patient's expression profile and polymorphisms to individualize drug therapy.

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Effect of Genetic Variation of NAT2 on Isoniazid and SLCO1B1 and CES2 on Rifampin Pharmacokinetics in Ghanaian Children with Tuberculosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02099-17 ◽

2017 ◽

Vol 62 (3) ◽

Cited By ~ 6

Author(s):

Albert Dompreh ◽

Xiaoli Tang ◽

Jianlin Zhou ◽

Hongmei Yang ◽

Ariel Topletz ◽

...

Keyword(s):

Organic Anion ◽

Organic Anion Transporter ◽

Pharmacokinetic Parameters ◽

Nucleotide Polymorphisms ◽

First Line ◽

Slow Acetylator ◽

Anion Transporter ◽

Transporter Family ◽

Essential Components ◽

The Relationship

ABSTRACT Isoniazid and rifampin are essential components of first-line antituberculosis (anti-TB) therapy. Understanding the relationship between genetic factors and the pharmacokinetics of these drugs could be useful in optimizing treatment outcomes, but this is understudied in children. We investigated the relationship between N-acetyltransferase type 2 ( NAT2 ) genotypes and isoniazid pharmacokinetics, as well as that between the solute carrier organic anion transporter family member 1B1 (encoded by SLCO1B1 ) and carboxylesterase 2 ( CES2 ) single nucleotide polymorphisms (SNPs) and rifampin pharmacokinetics in Ghanaian children. Blood samples were collected at times 0, 1, 2, 4, and 8 h postdose in children with tuberculosis on standard first-line therapy for at least 4 weeks. Isoniazid and rifampin concentrations were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and pharmacokinetic parameters were calculated using noncompartmental analysis. Genotyping of NAT2 , SLCO1B1 , and CES2 SNPs were performed using validated TaqMan genotyping assays. The Kruskal-Wallis test was used to compare pharmacokinetic parameters among the three genotypic groups and was followed by the Wilcoxon rank sum test for pairwise group comparisons. Genotype status inferred by the NAT2 4-SNP and 7-SNP genotyping panels identified children with a slow acetylator phenotype but not the rapid genotype. For rifampin, only the rare SLCO1B1*1b homozygous variant was associated with rifampin pharmacokinetics. Our findings suggest that NAT2 and SCLCO1B1*1b genotyping may have minimal clinical utility in dosing decisions at the population level in Ghanaian children, but it could be useful at the individual level or in populations that have a high frequency of implicated genotypes. Further studies in other populations are warranted.

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Lack of association between polymorphisms in the prostaglandin F2αreceptor and solute carrier organic anion transporter family 2A1 genes and intraocular pressure response to prostaglandin analogs

Ophthalmic Genetics ◽

10.3109/13816810.2011.628357 ◽

2011 ◽

Vol 33 (2) ◽

pp. 74-76 ◽

Cited By ~ 8

Author(s):

Catherine A. McCarty ◽

Richard Berg ◽

Richard Patchett ◽

Russell A. Wilke ◽

James K. Burmester

Keyword(s):

Intraocular Pressure ◽

Organic Anion ◽

Pressure Response ◽

Organic Anion Transporter ◽

Anion Transporter ◽

Transporter Family ◽

Solute Carrier

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SLCO4A1-AS1 Facilitates the Malignant Phenotype via miR-149-5p/STAT3 Axis in Gastric Cancer Cells

Journal of Oncology ◽

10.1155/2021/1698771 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Qing Li ◽

Dachuan Zhang ◽

Hui Wang ◽

Jun Xie ◽

Lei Peng ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Organic Anion ◽

Organic Anion Transporter ◽

Gastric Cancer Cells ◽

Anion Transporter ◽

Transporter Family ◽

Cancer Tissues ◽

Development Of Gastric Cancer

Solute carrier organic anion transporter family member 4A1 (SLCO4A1-AS1), a newly discovered lncRNA, may exert effects in tumors. Since its role in gastric cancer remains obscure, we sought to explore the mechanism of SLCO4A1-AS1 in gastric cancer. The relationship among SLCO4A1-AS1, miR-149-5p, and STAT3 was detected by bioinformatics, dual luciferase analysis, and Pearson’s test, and the expressions of these genes were determined by quantitative real-time PCR and Western blot. Moreover, CCK-8, flow cytometry, wound healing assay, and Transwell analysis were performed to verify the function of SLCO4A1-AS1 in gastric cancer. Rescue experiments were used to detect the role of miR-149-5p. The expressions of SLCO4A1-AS1 and STAT3 were increased, while the expression of miR-149-5p was suppressed in gastric cancer tissues and cell lines. In addition, STAT3 expression was negatively correlated with miR-149-5p expression but was positively correlated with SLCO4A1-AS1 expression. Overexpression of SLCO4A1-AS1 promoted cell viability, migration, invasion, and STAT3 expression but suppressed apoptosis, while knockdown of SLCO4A1-AS1 had the opposite effect. SLCO4A1-AS1 bound to miR-149-5p and targeted STAT3. Moreover, miR-149-5p mimic inhibited the malignant development of gastric cancer cells and obviously reversed the function of SLCO4A1-AS1 overexpression. Our research reveals that abnormally increased SLCO4A1-AS1 expression may be an important molecular mechanism in the development of gastric cancer.

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