ABCMdb

PMID: 17553166

Pasdar A, Yadegarfar G, Cumming A, Whalley L, St Clair D, MacLeod MJ
The effect of ABCA1 gene polymorphisms on ischaemic stroke risk and relationship with lipid profile.
BMC Med Genet. 2007 Jun 6;8:30., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCA1 p.Arg219Lys Methods: We studied four common polymorphisms in ABCA1 gene: G/A-L158L, G/A-R219K, G/ A-G316G and G/A-R1587K in 400 Caucasian ischaemic stroke patients and 487 controls. Login to comment 9 ABCA1 p.Arg219Lys Results: Genotype and allele frequencies of all polymorphisms were similar in cases and controls, except for a modest difference in the ABCA1 R219K allele frequency (P-value = 0.05). Login to comment 14 ABCA1 p.Arg219Lys Individuals who had R219K "22" genotype had a higher LDL level (p = 0.001). Login to comment 33 ABCA1 p.Arg219Lys ABCA1 p.Val771Met The only published study in ischaemic stroke on 244 Hungarian patients [25] suggests a protective role for the ABCA1-R219K and V771M polymorphisms. Login to comment 46 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys We used different sets of primers for each SNP as follows: 1- ABCA1-rs2230805 (G/A; L158L); designated as [ABCA1-6] ABCA1-2230805F: 5'-biotin-TAGACTTTGGGAGAGA- GAGGTTGT-3' ABCA1-2230805R: 5'-AATGAAACCTTCTCTGGGTTCC-3' 2- ABCA1-rs2234884 (G1051A; R219K); designated as [ABCA1-3] ABCA1-2234884F: 5'-biotin-AATTTCTGAGCTTTGT- GGACTA-3' ABCA1-2234884R: 5'-GCTCTGCTGCAGTCATTTTCTC-3' 3- ABCA1-rs2246841 (G888A; G316G); designated as [ABCA1-5] ABCA1-2246841F: 5'-biotin-TACCAGTTGAGAGACTT- GATCTTC-3' ABCA1-2246841R: 5'-TCTCGTATTGTCTGTGGGCATC-3' 4- ABCA1-rs1997618 (c/t, T1555I) ABCA1-1997618F: 5'-biotin-CCGAGTCAAGAAGTTAAT- GATGC-3' ABCA1-1997618R: 5'-GCTTTAGGTGTTTCTTCATTT- GTTT-3' 5- ABCA1-rs2234886 (G5155A; R1587K); designated as [ABCA1-4] ABCA1-2234886F: 5'-biotin-CAGCGGTTTACCTTGACAT- TATT-3' ABCA1-2234886R: 5'-GAAGATTTATGACAGGACT- GGACAC-3' 6- ABCA1-rs1883024 (c/t, P1648L) ABCA1-1883024F: 5'-biotin-TATACA- GACACAGCCACACTTA-3' ABCA1-1883024R: 5'-ATCTCACCAAGCAGCAGTTCTC-3' Of the six ABCA1 SNPs, only four SNPs (G/A-L158L, G/A-R219K, G/A-G316G and G/A-R1587K) were polymorphic in the Scottish population. Login to comment 59 ABCA1 p.Arg219Lys Haplotype frequencies for the four loci (G/A-L158L, G/A-R219K, G/A-G316G and G/A-R1587K) were estimated for cases and controls, using PHASE Ver.2.11 [28]. Login to comment 60 ABCA1 p.Arg219Lys Haplotype frequencies for the four loci (G/A-L158L, G/A-R219K, G/A-G316G and G/A-R1587K) were estimated for cases and controls, using PHASE Ver.2.11 [28]. Login to comment 62 ABCA1 p.Arg219Lys ABCA1-3 (G1051A; R219K) "G" allele frequency (R variant) was 68.2% in cases and 73.2% in controls (p = 0.05; OR = 0.79, 95%CI: 0.62-1.00), ABCA1-5 (G/A; G316G) "G" allele frequency (G variant) was 88% in cases and 86.7% in controls (p = 0.42; OR = 1.13, 95%CI: 0.84-1.52); ABCA1-4 (G5155A; R1587K) "G" allele frequency (R variant) was 77.4% in cases and 75.9% in controls (p = 0.47; OR = 1.09, 95%CI: 0.86-1.37). Login to comment 63 ABCA1 p.Arg219Lys ABCA1-3 (G1051A; R219K) "G" allele frequency (R variant) was 68.2% in cases and 73.2% in controls (p = 0.05; OR = 0.79, 95%CI: 0.62-1.00), ABCA1-5 (G/A; G316G) "G" allele frequency (G variant) was 88% in cases and 86.7% in controls (p = 0.42; OR = 1.13, 95%CI: 0.84-1.52); ABCA1-4 (G5155A; R1587K) "G" allele frequency (R variant) was 77.4% in cases and 75.9% in controls (p = 0.47; OR = 1.09, 95%CI: 0.86-1.37). Login to comment 64 ABCA1 p.Arg219Lys In addition to a trend to lower ABCA1-3 (G1051A; R219K) "G" allele frequency in all cases (p = 0.05), especially in males (p = 0.04), the "22" genotype was higher in LVD cases (p = 0.04) and also in patients over 65 years (p Table 2: Different stroke subtypes based on TOAST classification Subtype All Stroke Samples Number % Large Vessel Disease (LVD) 141 35.3% Small Vessel Disease (SVD) 98 24.5% Cardioembolic 76 19% Other/Unclear 85 21.3% Hemorrhagic Stroke 0 0 TOTAL 400 100% Table 1: Specifications of cases and controls Cases (n = 400) Controls (n = 487) Mean age (&#b1; SD)&#a7; 66 (&#b1; 11) 64.2(&#b1; 12.3) Sex (M:F Ratio)&#a7; 1.4 0.97 Hypertension*&#a7; 41% 18% Diabetes Mellitus**&#a7; 12.2% 3.2% Total Cholesterol mmol/l (Ave., SD)&#a7; 5.6 (&#b1; 1.3) 5.8 (&#b1; 1.2) HDL mmol/l (Ave., SD)&#a7; 1.2 (&#b1; 0.4) 1.4 (&#b1; 0.4) LDL mmol/l (Ave., SD) 3.5 (&#b1; 1.2) 3.5 (&#b1; 1.1) Total Triglyceride mmol/l (Ave., SD) 1.7 (&#b1; 1.1) 1.8 (&#b1; 1.1) Glucose mmol/l&#a7; 6.4 (&#b1; 2.4) 5.9 (&#b1; 1.2) * Hypertension defined as blood pressure > 160/90 mmHg or history of hypertension/on hypertensive therapy ** History of diabetes or confirmed laboratory diagnosis &#a7;Significant difference (P < 0.05) between cases and controls = 0.01), compared to controls. Login to comment 65 ABCA1 p.Arg219Lys In addition to a trend to lower ABCA1-3 (G1051A; R219K) "G" allele frequency in all cases (p = 0.05), especially in males (p = 0.04), the "22" genotype was higher in LVD cases (p = 0.04) and also in patients over 65 years (p Table 2: Different stroke subtypes based on TOAST classification Subtype All Stroke Samples Number % Large Vessel Disease (LVD) 141 35.3% Small Vessel Disease (SVD) 98 24.5% Cardioembolic 76 19% Other/Unclear 85 21.3% Hemorrhagic Stroke 0 0 TOTAL 400 100% Table 1: Specifications of cases and controls Cases (n = 400) Controls (n = 487) Mean age (± SD)§ 66 (± 11) 64.2(± 12.3) Sex (M:F Ratio)§ 1.4 0.97 Hypertension*§ 41% 18% Diabetes Mellitus**§ 12.2% 3.2% Total Cholesterol mmol/l (Ave., SD)§ 5.6 (± 1.3) 5.8 (± 1.2) HDL mmol/l (Ave., SD)§ 1.2 (± 0.4) 1.4 (± 0.4) LDL mmol/l (Ave., SD) 3.5 (± 1.2) 3.5 (± 1.1) Total Triglyceride mmol/l (Ave., SD) 1.7 (± 1.1) 1.8 (± 1.1) Glucose mmol/l§ 6.4 (± 2.4) 5.9 (± 1.2) * Hypertension defined as blood pressure > 160/90 mmHg or history of hypertension/on hypertensive therapy ** History of diabetes or confirmed laboratory diagnosis §Significant difference (P < 0.05) between cases and controls = 0.01), compared to controls. Login to comment 69 ABCA1 p.Arg219Lys Cases with ABCA1-3 (G1051A; R219K) "22" genotype had a higher LDL level compared to controls which remained significant after Bonferroni correction (p = 0.003). Login to comment 70 ABCA1 p.Arg219Lys Cases with ABCA1-3 (G1051A; R219K) "22" genotype had a higher LDL level compared to controls which remained significant after Bonferroni correction (p = 0.003). Login to comment 71 ABCA1 p.Arg219Lys However, in this subgroup, females with ABCA1-3 (G1051A; R219K) "11" and ABCA1-4 (G5155A; R1587K) "22" genotypes had a higher level of IDL (p = 0.01 and p = 0.02) respectively. Login to comment 72 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys However, in this subgroup, females with ABCA1-3 (G1051A; R219K) "11" and ABCA1-4 (G5155A; R1587K) "22" genotypes had a higher level of IDL (p = 0.01 and p = 0.02) respectively. Login to comment 73 ABCA1 p.Arg219Lys Effects of alleles on lipid profile Comparing the lipid profiles in carriers of different ABCA1 alleles revealed that individuals who were the ABCA1-R219K carrier (K allele) had a lower TG level than non carriers (p = 0.005). Login to comment 83 ABCA1 p.Arg219Lys Other works have reported that CAD patients who are carriers of R219K allele had less severe atherosclerosis [31] and overall lower risk of CAD [36]. Login to comment 84 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys Other works have reported that CAD patients who are carriers of R219K allele had less severe atherosclerosis [31] and overall lower risk of CAD [36]. Login to comment 85 ABCA1 p.Arg219Lys Andrikovics et al recently reported a higher frequency of R219K in controls than in Hungarian stroke patients and suggested a protective role for this polymorphism [25]. Login to comment 88 ABCA1 p.Arg219Lys While the R219K -G1051A- (A or "K" variant) has been associated with decreased TG, increased HDL and subsequently a lower risk for atherosclerotic progression, in contrast the R allele has been associated with vascular disease [31]. Login to comment 89 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys While the R219K -G1051A- (A or "K" variant) has been associated with decreased TG, increased HDL and subsequently a lower risk for atherosclerotic progression, in contrast the R allele has been associated with vascular disease [31]. Login to comment 90 ABCA1 p.Arg219Lys This has not been confirmed in our study, although in our stroke population those with R219K "22" genotype (AA) had a higher level of LDL and the "K allele" carriers had a lower TG. Login to comment 91 ABCA1 p.Arg219Lys The HDL level showed no significant difference among different R219K genotypes. Login to comment 92 ABCA1 p.Arg219Lys The HDL level showed no significant difference among different R219K genotypes. Login to comment 101 ABCA1 p.Arg219Lys Other studies have shown an association between the R219K polymorphism and MI, but no association between haplotype arrangements and MI. Login to comment 102 ABCA1 p.Arg219Lys Other studies have shown an association between the R219K polymorphism and MI, but no association between haplotype arrangements and MI. Login to comment 111 ABCA1 p.Arg219Lys Among the studied ABCA1 gene polymorphisms, R219K has the greatest impact on lipid profile especially LDL and TG. Login to comment 112 ABCA1 p.Arg219Lys Among the studied ABCA1 gene polymorphisms, R219K has the greatest impact on lipid profile especially LDL and TG. Login to comment