ABCMdb

PMID: 18621447

Wang N, Xue XH, Lin Y, Fang L, Murong S, Wu ZY
The R219K polymorphism in the ATP-binding cassette transporter 1 gene has a protective effect on atherothrombotic cerebral infarction in Chinese Han ethnic population.
Neurobiol Aging. 2010 Apr;31(4):647-53. Epub 2008 Jul 14., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Val825Ile Neurobiology of Aging 31 (2010) 647-653 The R219K polymorphism in the ATP-binding cassette transporter 1 gene has a protective effect on atherothrombotic cerebral infarction in Chinese Han ethnic population Ning Wanga, Xie-Hua Xuea, Yi Lina, Ling Fanga, Shenxing Muronga, Zhi-Ying Wua,b,* a Department of Neurology and Institute of Neurology, First Affiliated Hospital, Center of Neuroscience, Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, China b Department of Neurology and Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 12 Wulumuqi Middle Road, Shanghai 200040, China Received 30 November 2007; received in revised form 29 April 2008; accepted 28 May 2008 Available online 14 July 2008 Abstract The association of R219K and V825I polymorphisms of ABCA1 gene with cerebral infarction has been rarely reported. Login to comment 3 ABCA1 p.Arg219Lys ABCA1 p.Val825Ile Genotyping of R219K and V825I were performed by PCR-RFLP analysis. Login to comment 5 ABCA1 p.Arg219Lys The R219K genotype frequency distributions were significantly different between patients with atherothrombotic cerebral infarction (ACI) and control individuals, with fewer KK genotypes and more RR genotypes in ACI patients (χ2 = 9.89, P < 0.01). Login to comment 8 ABCA1 p.Arg219Lys These results indicate that the K allele of R219K polymorphism is an independent protective factor against ACI. Login to comment 9 ABCA1 p.Val825Ile In addition, though there is no association of V825I with ACI, this polymorphism may have certain synergistic effect with hypertension in susceptibility to ACI. Login to comment 11 ABCA1 p.Arg219Lys ABCA1 p.Val825Ile Keywords: Cerebral infarction; ATP-binding cassette transporter 1; R219K; V825I 1. Login to comment 19 ABCA1 p.Arg219Lys ABCA1 p.Val825Ile The more common SNPs are R219K in exon 7 and V825I in exon 17. Login to comment 23 ABCA1 p.Arg219Lys Besides, there was a report that KK individuals had a higher level of LDL-C and the K allele carriers had a lower TG (Pasdar et al., 2007) and another report that R219K did not influence the plasma lipids levels (Takagi et al., 2002). Login to comment 26 ABCA1 p.Arg219Lys ABCA1 p.Val825Ile Taken together, these controversial findings indicate that the function of R219K and V825I may be significant in certain environmental factors and population backgrounds. Login to comment 27 ABCA1 p.Arg219Lys ABCA1 p.Val825Ile Although the association of R219K and/or V825I with CAD has been widely reported in different ethnic populations, the association of them with cerebral infarction has been reported rarely (Andrikovics et al., 2006; Pasdar et al., 2007). Login to comment 30 ABCA1 p.Arg219Lys ABCA1 p.Val825Ile The aim of this study is to investigate the association of R219K and V825I with cerebral infarction and levels of plasma lipids in the Han ethnic group in Chinese population. Login to comment 55 ABCA1 p.Val825Ile ABCA1 p.Val825Ile ABCA1 p.Val825Ile Genotyping of R219K and V825I Genotyping of R219K (primers: 5 -AAAGACTTCAA- GGACCCAG-3 and 5 -ACAAAGTCATGCTGTCCAAG- 3 ) and V825I (primers: 5 -GAGACTGACCAGGAAATGG- 3 and 5 -ATGCACTGCAGAGATTCTAG-3 ) was performed by PCR-RFLP analysis. Login to comment 56 ABCA1 p.Val825Ile PCR product was digested with EcoNI for R219K and BsaI for V825I according to the manufacturer`s recommendations (New England Biolabs, Beverly, MA, USA), then followed by a 2.5% agarose gel electrophoresis. Login to comment 58 ABCA1 p.Val825Ile Statistical analysis A chi-square analysis was performed to determine the Hardy-Weinberg equilibrium of R219K and V825I in the groups. Login to comment 60 ABCA1 p.Val825Ile The influence of R219K and V825I on plasma lipids were evaluated using analysis of variance with genotype as group variable and total cholesterol, triglycerides, HDL-C, LDL-C, ApoA1 and ApoB as dependent variables. Login to comment 63 ABCA1 p.Val825Ile ABCA1 p.Val825Ile * P < 0.05 Table 2 Genotype and allele frequency distributions of R219K and V825I R219K V825I Control ACI LI Control ACI LI All n = 152 (%) n = 193 (%) n = 131 (%) n = 152 (%) n = 193 (%) n = 131 (%) RR 41 (26.97) 75 (38.86) 32 (24.43) VV 41 (26.97) 45 (23.32) 39 (29.77) RK 77 (50.66) 96 (49.74) 76 (58.01) VI 76 (50.00) 110 (57.00) 71 (54.20) KK 34 (22.37) 22 (11.40)* 23 (17.56) II 35 (23.03) 38 (19.69) 21 (16.03) R frequency 52.3 63.73 53.43 V frequency 51.97 51.81 56.87 K frequency 47.7 36.27** 46.57 I frequency 48.03 48.19 43.13 Male n = 97 (%) n = 136 (%) n = 81 (%) n = 97 (%) n = 136 (%) n = 81 (%) RR 28 (28.86) 51 (37.50) 22 (27.16) VV 28 (28.86) 31 (22.80) 20 (24.69) RK 41 (42.28) 71 (52.21) 44 (54.32) VI 42 (43.30) 76 (55.88) 49 (60.49) KK 28 (28.86) 14 (10.29)** 15 (18.52) II 27 (27.84) 29 (21.32) 12 (14.82) R frequency 50 63.6 54.32 V frequency 50.52 50.09 54.94 K frequency 50 36.40** 45.68 I frequency 49.48 49.24 45.06 Female n = 55 (%) n = 57 (%) n = 50 (%) n = 55 (%) n = 57 (%) n = 50 (%) RR 13 (23.64) 24 (42.11) 10 (20.00) VV 13 (23.64) 14 (24.56) 19 (38.00) RK 36 (65.45) 25 (43.86) 32 (64.00) VI 34 (61.82) 34 (59.65) 22 (44.00) KK 6 (10.91) 8 (14.03) 8 (16.00) II 8 (15.54) 9 (15.79) 9 (18.00) R frequency 56.36 64.04 52 V frequency 54.55 54.39 60 K frequency 43.64 35.97 48 I frequency 45.45 45.61 40 <60 years n = 78 (%) n = 56 (%) n = 37 (%) n = 78 (%) n = 56 (%) n = 37 (%) RR 24 (30.77) 23 (41.07) 15 (40.54) VV 20 (25.64) 14 (25.00) 10 (22.73) RK 41 (52.56) 25 (44.64) 17 (45.95) VI 37 (47.44) 32 (57.14) 21 (47.73) KK 13 (16.67) 8 (14.29) 5 (13.51) II 21 (26.92) 10 (17.86) 6 (13.64) R frequency 57.05 63.39 63.51 V frequency 49.36 53.57 55.41 K frequency 42.95 36.61 36.49 I frequency 50.64 46.43 45.59 ≥60 years n = 74 (%) n = 137 (%) n = 94 (%) n = 74 (%) n = 137 (%) n = 94 (%) RR 17 (22.97) 52 (37.96) 20 (21.28) VV 21 (28.39) 31 (22.63) 29 (30.85) RK 36 (48.65) 71 (51.82) 56 (59.57) VI 39 (52.70) 78 (56.93) 50 (53.19) KK 21 (28.39) 14 (10.22)* 18 (19.15) II 14 (18.91) 28 (20.44) 15 (15.96) R frequency 46.30 63.87 51.06 V frequency 54.73 51.09 57.45 K frequency 52.70 36.13* 48.94 I frequency 45.27 48.91 42.55 ACI, atherothrombotic cerebral infarction; LI, lacunar infarction; *P < 0.01, **P < 0.005. culated. Login to comment 75 ABCA1 p.Val825Ile Genotype and allele frequency distributions R219K and V825I were in Hardy-Weinberg equilibrium in the ACI, LI and control groups (P > 0.05, see Supplemental data). Login to comment 84 ABCA1 p.Val825Ile In addition, V825I was not associated with absence/presence of ACI or LI. Login to comment 89 ABCA1 p.Val825Ile The interaction between R219K/V825I and risk factors was showed in Table 5. Login to comment 91 ABCA1 p.Val825Ile * P < 0.05 Table 5 The interaction among R219K, V825I and risk factors Genotypes and RF P OR 95% CI KK and hypertension Reference RK and hypertension* 0.002 3.09 1.54-6.19 RR and hypertension* 0.001 4.81 1.94-11.94 KK and DM2 Reference RK and DM2 0.108 2.822 0.79-10.01 RR and DM2 0.99 0.00 0.00 II and hypertension Reference VI and hypertension* 0.001 3.91 1.93-7.93 VV and hypertension* 0.04 2.42 1.04-5.62 II and DM2 Reference VI and DM2 0.105 2.33 0.64-9.91 VV and DM2 0.406 1.963 0.400-9.648 KK and II Reference RR and VI* 0.003 2.69 1.39-5.22 RR and VV 0.52 1.36 0.53-3.45 RK and VI 0.56 1.17 0.69-1.99 RK and VV 0.56 1.23 0.61-2.49 DM2, diabetes mellitus type 2; RF, risk factor. Login to comment 94 ABCA1 p.Val825Ile There was no interaction between R219K/V825I and diabetes mellitus 2 (DM2). Login to comment 97 ABCA1 p.Val825Ile This result further confirms that there is no association between V825I and ACI. Login to comment 107 ABCA1 p.Val825Ile In addition, there was no association between V825I and lipids levels. Login to comment 108 ABCA1 p.Val825Ile Table 6 Association of R219K and V825I with plasma lipid levels Lipid All Male Female RR n = 148 RK n = 249 KK n = 79 RR n = 101 RK + KK n = 213 RR n = 47 RK + KK n = 115 BMI (kg/m2) 23.35 ± 2.76 23.60 ± 2.46 23.62 ± 2.42 23.34 ± 2.94 23.65 ± 2.26 Hypertension (%) 43.24 46.18 37.97 43.56 45.07 42.55 42.61 DM2 (%) 11.49 12.05 13.92 9.9 13.15 14.89 11.3 Smoking (%) 8.78 6.43 7.6 12.87 9.39 0 1.74 Alcohol (%) 4.05 3.21 3.80 3.96 4.23 4.26 1.74 TC 4.79 ± 0.95 4.85 ± 1.07 4.88 ± 0.93 4.74 ± 0.87 4.68 ± 0.94 4.90 ± 1.12 5.23 ± 1.11 TG 1.78 ± 0.96 1.74 ± 0.98 1.53 ± 0.61* 1.79 ± 1.05 1.67 ± 0.97 1.75 ± 0.68 1.70 ± 0.99 HDL-C 1.07 ± 0.29 1.11 ± 0.30 1.12 ± 0.31 1.07 ± 0.29 1.05 ± 0.29 1.05 ± 0.03 1.22 ± 0.29**** LDL-C 3.03 ± 0.87 3.03 ± 0.92 2.98 ± 0.77 2.98 ± 0.79 2.86 ± 0.79 3.16 ± 1.04 3.32 ± 0.98 ApoA1 1.12 ± 0.24 1.18 ± 0.22** 1.22 ± 0.24*** 1.13 ± 0.24 1.14 ± 023 1.10 ± 0.25 1.28 ± 0.19**** ApoB 1.02 ± 0.28 1.06 ± 0.29 1.02 ± 0.24 1.00 ± 0.25 1.02 ± 0.28 1.05 ± 0.33 1.10 ± 0.27 Lipids VV n = 125 VI n = 257 II n = 94 VV + VI n = 246 II n = 68 VV + VI n = 136 II n = 26 BMI (kg/m2) 24.50 ± 2.75 23.17 ± 2.36 23.24 ± 2.47 23.59 ± 2.49 23.43 ± 2.47 23.62 ± 2.77 22.01 ± 2.60 Hypertension (%) 44.80 44.36 41.49 44.71 39.71 44.12 46.15 DM2 (%) 12.8 10.9 14.89 11.79 14.71 11.03 15.38 Smoking (%) 7.20 7.78 6.38 9.76 8.82 3.68 0 Alcohol (%) 2.40 3.89 4.26 2.44 4.41 2.21 3.84 TC 4.82 ± 0.99 4.91 ± 0.99 4.66 ± 1.06 4.72 ± 0.89 4.62 ± 0.99 5.17 ± 1.09 4.83 ± 1.36 TG 1.67 ± 0.92 1.70 ± 0.96 1.75 ± 0.91 1.71 ± 1.01 1.73 ± 0.95 1.7 ± 0.93 1.84 ± 0.76 HDL-C 1.12 ± 0.29 1.1 ± 0.30 1.05 ± 0.33 1.06 ± 0.28 1.05 ± 0.34 1.19 ± 0.30 1.04 ± 0.30 LDL-C 3.04 ± 0.92 3.06 ± 0.82 2.86 ± 0.96 2.95 ± 0.77 2.75 ± 0.85 3.27 ± 0.97 3.38 ± 1.26 ApoA1 1.19 ± 0.22 1.17 ± 0.23 1.12 ± 0.26 1.14 ± 0.23 1.12 ± 0.25 1.24 ± 0.21 1.14 ± 0.31 ApoB 1.04 ± 0.30 1.06 ± 0.26 1.01 ± 0.32 1.03 ± 0.26 0.97 ± 0.31 1.09 ± 0.28 1.11 ± 0.34 *P = 0.06, **P = 0.046, ***P = 0.03, ****P = 0.01. Login to comment 111 ABCA1 p.Arg219Lys R219K is located in the extracellular loop of the ABCA1 protein, and plays an important role for the interaction of ApoA1 and cholesterol efflux. Login to comment 112 ABCA1 p.Val825Ile V825I is located in the middle part of the protein corresponding to the sixth transmembrane ␣-helix. Login to comment 115 ABCA1 p.Arg219Lys R219K is the most common polymorphism of ABCA1 and the allele frequency of the K allele is 26-46% in Caucasian population (Koren-Morag et al., 2002; Pasdar et al., 2007; Singaraja et al., 2003). Login to comment 116 ABCA1 p.Arg219Lys To date, several studies have reported controversial results about the possible role of R219K in arteriosclerosis. Login to comment 119 ABCA1 p.Arg219Lys They concluded that observed effects were independent of any other SNPs found in association with R219K (Clee et al., 2001). Login to comment 123 ABCA1 p.Arg219Lys In our present study, R219K was 47.70% in control group, similar to that of Caucasian population (Singaraja et al., 2003). Login to comment 124 ABCA1 p.Arg219Lys In addition, the K allele of R219K was associated with increased HDL-C and apoA1 levels in the female subgroup. Login to comment 126 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Although the association of R219K with CAD has been widely studied in different ethnic populations, the association of R219K with cerebral infarction has been reported rarely. Login to comment 127 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Although the association of R219K with CAD has been widely studied in different ethnic populations, the association of R219K with cerebral infarction has been reported rarely. Login to comment 131 ABCA1 p.Val825Ile This result is consistent with that of Andrikovics et al. but contrary to that of Pasdar et al. The data about the association of V825I with lipids levels are controversial. Login to comment 132 ABCA1 p.Val825Ile ABCA1 p.Val825Ile This result is consistent with that of Andrikovics et al. but contrary to that of Pasdar et al. The data about the association of V825I with lipids levels are controversial. Login to comment 133 ABCA1 p.Val825Ile Both Clee et al. and Tan et al. reported that there was no association of V825I with lipids levels (Clee et al., 2001; Tan et al., 2003). Login to comment 134 ABCA1 p.Val825Ile However, our results did not exhibit any association of V825I with lipids levels and cerebral infarction. Login to comment 135 ABCA1 p.Val825Ile ABCA1 p.Val825Ile However, our results did not exhibit any association of V825I with lipids levels and cerebral infarction. Login to comment 136 ABCA1 p.Arg219Lys ABCA1 p.Val825Ile ABCA1 p.Val825Ile This may be due to the substitution of V825I is conservative and the polymorphism may only exert minimal influence on cholesterol efflux activity (Tan et al., 2003). Login to comment 137 ABCA1 p.Arg219Lys ABCA1 p.Val825Ile There was few report associated with the synergistic effects among R219K, V825I and risk factors. Login to comment 140 ABCA1 p.Val825Ile Although there is no association of V825I with ACI, this polymorphism may have certain synergistic effect with hypertension in susceptibility to ACI. Login to comment 141 ABCA1 p.Val825Ile Although there is no association of V825I with ACI, this polymorphism may have certain synergistic effect with hypertension in susceptibility to ACI. Login to comment