ABCMdb

PMID: 19341173

Ksiazek J, Ciechanowicz A, Wierzbicka A, Syczewska M, Grenda R
Is dyslipidemia sustained during remission of nephrotic syndrome genetically determined? Evaluation of genetic polymorphisms of proteins involved in lipoprotein metabolism in children and adolescents with nephrotic syndrome.
Pol Arch Med Wewn. 2009 Jan-Feb;119(1-2):11-6., [PubMed]

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No. Mutations Sentence Comment

8 ABCA1 p.Val825Ile ABCA1 p.Val771Met We evalauated associations between lipid profile and genetic polymorphisms, V771M, V825I, and R1587K of the gene encoding the cassette ABCA1 (adenosine triphosphate binding cassette transporter A1) protein synthesis, a b5;3 polymorphism of the gene encoding the type b5; of apolipoprotein E (apoE) synthesis and that of the gene encoding the cholesterol ester transfer protein (CETP) synthesis. Login to comment 9 ABCA1 p.Val825Ile Resultsߓ Dyslipidemia was observed in 10/13 (76.9%) patients with V825I polymorphism vs. 27/37 (73%) of nonߛcarriers, and in 16/21 (76.2%) patients with R1587K polymorphism vs. 21/29 (72.4%) in the remaining subjects. Login to comment 10 ABCA1 p.Val771Met V771M polymorphism was found only in 2 (4%) patients and one subject had abnormal lipid profile. Login to comment 36 ABCA1 p.Val825Ile ABCA1 p.Val771Met Some investigators have suggestߛ ed higher incidence of specific genotypes in paߛ tients with nephritic syndrome and endߛstage Table 1ߓ Characteristics of patients Patients Total Males Females Steroidߛresistant Number (n) % ߗ 50 100 35 70 15 30 12 24 Mean age (years) SD ߗ 10.45 ߗߗ 3.04 10.5 ߗ 3.13 10.35 ߗ 2.82 Duration of treatment (years) SD ߗߗ 7.09 ߗߗ 2.88 ߗ 6.88 ߗ 3.14 ߗ 7.55 ߗ 2.19 Histological diagnosis MCNS ߗ 21 14 ߗ 7 ߗ 1 MPGN ߗ 26 19 ߗ 7 ߗ 9 FSGS ߗߗ 3 ߗ 1 ߗ 2 ߗ 2 Abbreviations: FSGS - focal segmental glomerulosclerosis, MCNS - minimal change nephrotic syndrome, MPGN - mesangial proliferative glomerulonephritis, SD - standard deviation of the ABCA1 gene (V771M, V825I and R1587K), a polymorphism of the CETP gene and polymorߛ phisms of the apoE gene. Login to comment 39 ABCA1 p.Val825Ile ABCA1 p.Val825Ile ABCA1 p.Val771Met ABCA1 p.Val771Met Three single nuߛ cleotide variants of guanine (G) > adenine (A) transition of the ABCA1 gene such as V771M, V825I i R1587K that determine the HDLߛC plasma level were genotyped by the selfߛdevelߛ oped method, using the restriction enzyme Tail for determining polymorphism V771M, the reߛ striction enzyme MboI for polymorphism V825I and the restriction enzyme Bgl II for R1587K polymorphism. Login to comment 41 ABCA1 p.Val825Ile Transition G to A in posiߛ tion 2472 cDNA caused substitution of valine to isoleucine in position 825 of the polypepߛ tide chain of ABCA1 protein (polymorphism V825IߛG2472A). Login to comment 56 ABCA1 p.Val825Ile ABCA1 p.Val771Met The results were assessed in comparison with normal reference values coming from the evaluߛ ation of the healthy Warszawa population aged between 6 and 20, published previously by inߛ vestigators from the Children`s Memorial Health Institute.14 In all subjects the following genetic polyߛ morphisms were evaluated: - three nonߛsynonߛ ymous single nucleotide polymorphisms variants Table 2ߓ Median values of lipid profile parameters in patients with dyslipidemia (nߙ=ߙ37) and normolipidemia (nߙ=ߙ13) during remission of nephrotic syndrome Parameter mg/dl nߙ=ߙ13 nߙ=ߙ37 pa TC (mg/dl) 175.8 232 <0.0001 HDLߛC (mg/dl) ߗ 55 ߗ 49 NS LDLߛC (mg/dl) 100.66 163.29 <0.0001 VLDLߛC (mg/dl) ߗ 14.2308 ߗ 21.6 0.0015 TG (mg/dl) ߗ 77.2222 156.25 0.00007 ApoB (g/dl) ߗߗ 0.8067 ߗߗ 1.22 0.000004 ApoA1 (g/dl) ߗߗ 1.52 ߗߗ 1.51 NS OxyߛLDL (mU/ml) 278.28 504.9 0.0022 GPX (u/gHb) ߗ 32.30 ߗ 30.71 0.0016 Lp(a) (mg/dl) ߗ 10.20 ߗ 15.62 0.0184 Albumin (g/l) ߗ 40.73 ߗ 37.52 0.0014 aߓ MannߛWhitney`s test Abbreviations: apoA1 - apolipoprotein A1, apoB - apolipoprotein B, GPX - glutathione peroxidase, HDLߛC - highߛdensity lipoprotein cholesterol, LDLߛC - lowߛdensity lipoprotein cholesterol, Lp (a) - lipoprotein (a), NS - not significant, oxyߛLDLߛC - oxidized LDLߛcholesterol, TC - total cholesterol, TG - triglycerides, VLDLߛC - very lowߛdensity lipoprotein cholesterol Table 3ߓ Number of patients with ABCA1 genetic polymorphisms Patients Polymorphic variants V771M V825I R1587K V825 Iߙ+ߙR1587K GA GA AA GA AA GAߛGA GAߛAA s - d. ns nߙ=ߙ38 2 ߗ 9 1 11 2 5 1 s - r. ns nߙ=ߙ12 - ߗ 3 - ߗ 6 2 2 1 Overall nߙ=ߙ50 2 (4%) 13 (26%) 21 (42%) 9 (18%) Abbreviations: AA, GA, GG - variants of polymorphism of ABCA1 gene, sߛd ns - steroidߛdependent nephrotic syndrome, sߛr ns - steroidߛresistant nephrotic syndrome, in TABLE 3. Login to comment 57 ABCA1 p.Val771Met The V771M of ABCA1 gene polymorߛ phism of GA variant was confirmed in 2 (4%) paߛ tients. Login to comment 58 ABCA1 p.Val825Ile The V825I polymorphism of ABCA1 gene of GA variant was confirmed in 12 of 50 (24%) cases. Login to comment 59 ABCA1 p.Val825Ile The V825I polymorphism of AA variant was confirmed in 1/50 (2%) case with the low HDLߛC serum level. Login to comment 60 ABCA1 p.Val825Ile Overall, the V825I polyߛ morphism was demonstrated in 13 of 50 (26%) patients. Login to comment 65 ABCA1 p.Val825Ile The presence of 2 gene polymorphisms (V825I and R1587K) was detected in 9 of 50 (18%) patients. Login to comment 70 ABCA1 p.Val825Ile Among 13 subjects with confirmed V825I polyߛ morphisms, abnormal lipid profile was shown in the majority of cases (10; 76.9%). Login to comment 81 ABCA1 p.Val825Ile ABCA1 p.Val825Ile ABCA1 p.Val771Met ABCA1 p.Val771Met ABCA1 p.Arg587Lys The number and distribution of specific gene polymorphisms of ABCA1 are presented Table 4ߓ Distribution of significant (compared to reference data) lipid abnormalities in subgroups of patients divided with regard to ABCA1 genetic polymorphisms Polymorphism Disturbances V771M nߙ=ߙ2 (4%) V825I nߙ=ߙ13 (26%) R1587K nߙ=ߙ21 (42%) V8251ߙ+ߙR1587K nߙ=ߙ9 (18%) GA nߙ=ߙ2 AA GA nߙ=ߙ12 AA nߙ=ߙ1 GA nߙ=ߙ17 AA nߙ=ߙ4 GAߛGA nߙ=ߙ7 GAߛAA nߙ=ߙ2 ࢏ TC - - 1 - 2 - 1 - ࢏ TCߙ+ߙ࢏ TG 1 - 2 - 3 1 2 2 ࢏TCߙ+ߙ࢏ TGߙ+ߙ࢑ HDLߛC - - 2 - 4 1 1 - ࢏TCߙ+ߙ࢑ HDLߛC - - 1 - - 1 - - ࢏ TGߙ+ߙ࢑ HDLߛC - - 1 - 1 1 - ߙ+ߙ࢑ HDLߛC - - 2 1 2 1 1 - Overall 1 50% - 10 76.9% 16 76.2% 7 77.8% No disturbances 1 50% - 3 23.1% 5 33.8% 2 22.2% Abbreviations: AA, GA, GG - variants of polymorphism of ABCA1 gene, HDLߛC - fraction HDL of cholesterol, TC - total cholesterol, ߓ TG - triglycerides, V771M, V825I, R587K - nonߛsynonymous single nucleotide polymorphisms of ABCA1 cassette gene Table 5ߓ Distribution of significant (compared to reference data) lipid abnormalities in subgroups of patients divided with regard to CETP gene polymorphisms Polymorphism Disturbances GA variant nߙ=ߙ25 (50%) AA variant nߙ=ߙ6 (12%) ࢏ TCߙ+ߙTG 3 2 ࢏TCߙ+ߙTGߙ+ߙ࢑ HDLߛC 3 2 ࢏ TGߙ+ߙ࢑ HDLߛC 1 - ࢏ TCߙ+ߙ࢑ HDLߛC 1 - ࢏ TC 4 1 - ࢑ HDLߛC 4 1 Overall 22/31 71% No lipid disturbances 9/31 29% Abbreviations: AA, GA, GG - variants of polymorphism of the gene, HDLߛC - fraction HDL of cholesterol, TC - total cholesterol, TG - triglycerides was a nonߛsignificant trend (pߙ=ߙ0.067) in terms of association between the triglyceride level and R1587K genotype. Login to comment 100 ABCA1 p.Val825Ile ABCA1 p.Val771Met There Table 6ߓ Distribution of significant (compared to reference data) lipid abnormalities in subgroups of patients divided with regard to apoE gene polymorphisms Lipid disturbances ApoE subtype b5;3b5;3 nߙ=ߙ35 (70%) b5;3b5;4 nߙ=ߙ6 b5;2b5;3 nߙ=ߙ5 b5;2b5;4 nߙ=ߙ1 b5;4b5;4 nߙ=ߙ2 b5;2b5;2 nߙ=ߙ1 ࢏TCߙ+ߙ࢏TGߙ+ߙ࢑ HDLߛC ߗ 4 2 2 1 - - ࢏TGߙ+ߙ࢑HDLߛC ߗ 1 - - - 1 - ࢑ HDLߛC ߗ 5 1 1 - - 1 ࢏TC ߗ 7 1 - - - - ࢏TCߙ+ߙ࢏TG ߗ 7 1 - - - - ࢏TCߙ+ߙ࢑ HDLߛC ߗ 2 - - - - - Overall 26 (74.3%) 5 3 1 1 1 No disturbances ߗ 9 (25.7%) 1 2 - 1 - Abbreviations: apoE - apolipoprotein E, HDLߛC - fraction HDL of cholesterol, TC - total cholesterol, TG - triglycerides Table 7ߓ Distribution of lipid disturbances prevalence in children with and without specific genetic polymorphisms(summary) Polymorphism Number of patients (n) with polymorphisms and lipid abnormalities with no polymorphisms and lipid abnormalities V771M nߙ=ߙ2/50 1/2 (50%) 36/48 (76.6%) V825I nߙ=ߙ13/50 10/13 (76.9%) 27/37 (73%) R1587K nߙ=ߙ21/50 16/21 (76.2%) 21/29 (72.4%) CETP nߙ=ߙ31/50 22/31 (71%) 15/19 (78.9%) apo b5;3b5;3 nߙ=ߙ35/50 26/35 (74.35) - Other types apoE nߙ=ߙ15/50 12/15 (73.3%) - Abbreviations: apoE- polymorphism of apoE gene, CETP - polymorphism of CETP gene, 14ߓ Litwin M, a;ladowska J, Antoniewicz J, et al.: Metabolic abnormalities, insulin resistance and metabolic syndrome in children with primary hyperߛ tension. 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