ABCMdb

PMID: 21420943

Daniil G, Phedonos AA, Holleboom AG, Motazacker MM, Argyri L, Kuivenhoven JA, Chroni A
Characterization of antioxidant/anti-inflammatory properties and apoA-I-containing subpopulations of HDL from family subjects with monogenic low HDL disorders.
Clin Chim Acta. 2011 Jun 11;412(13-14):1213-20. Epub 2011 Mar 21., [PubMed]

Sentences

No. Mutations Sentence Comment

56 ABCA1 p.Cys1477Arg ABCA1 p.Cys1477Arg ABCA1 p.Asn1800His ABCA1 p.Gln1038* ABCA1 p.Leu1056Pro Subjects We examined serum obtained from 3 heterozygotes for the apoA-I (NM_000039) mutation p.L202P (n=3; mutation was previously denoted as L178P [14]), 6 heterozygotes for ABCA1 (NM_005502) mutations(p.C1477R,n=3;p.L1056P,n=3),2compoundheterozygotes for ABCA1 mutations (p.C1477R/IVS25+1GNC; p.Q1038X/p.N1800H), 1 homozygote for the ABCA1 mutation p.L1056P, 12 heterozygotes for LCAT (NM_000229) mutations (p.P34Q, n=1; p.Y107X, n=1; p.T147I, n=4; p.N155D, n=2; p.I202T, n=1; p.R322C, n=2, p.V333M, n=1), 3 compound heterozygotes for the LCAT mutation p.T147I/IVS4-22TNC and 1 homozygote for the LCAT mutation p.N155D. Login to comment 147 ABCA1 p.Cys1477Arg ABCA1 p.Asn1800His ABCA1 p.Gln1038* Male/female TC HDL-c apoA-I apoA-II LDL-c apoB TG apoA-I mutation carriers Unaffected (n=3) 1/2 179&#b1;27 45&#b1;3 163&#b1;13 30&#b1;1 131&#b1;22 97&#b1;15 97&#b1;25 Heterozygotes (n=3) 1/2 141&#b1;12* 20&#b1;14* 87&#b1;38* 19&#b1;6* 113&#b1;5 85&#b1;6 97&#b1;45 ABCA1 mutation carriers Unaffected (n=8) 4/4 171&#b1;56 57&#b1;15 160&#b1;29 30&#b1;4 111&#b1;23 84&#b1;12 85&#b1;20 Heterozygotes (n=6) 3/3 179&#b1;64 37&#b1;7** 124&#b1;12** 28&#b1;2 129&#b1;35 98&#b1;22 90&#b1;44 Compound heterozygote 1c (n=1) 1/0 54 6 4 2 44 75 138 Compound heterozygote 2d (n=1) 0/1 220 3 7 ndb 173 192 387 Homozygote (n=1) 0/1 63 0.8 nd nd 61 81 87 LCAT mutation carriers Unaffected (n=7) 5/2 199&#b1;32 49&#b1;13 166&#b1;19 31&#b1;2 134&#b1;28 100&#b1;20 123&#b1;58 Heterozygotes (n=12) 8/4 166&#b1;47 32&#b1;11** 122&#b1;27*** 26&#b1;5* 122&#b1;38 97&#b1;28 115&#b1;49 Compound heterozygotes (n=3) 0/3 140&#b1;24* 5&#b1;1*** 48&#b1;8*** 3.8&#b1;0.3*** 118&#b1;17 102&#b1;27 244&#b1;103* Homozygote (n=1) 1/0 107 3 58 4 77 118 279 a Values presented as mean&#b1;SD (mg/dl); b nd, not detectable; c ABCA1[p.C1477R/IVS25+1GNC]; d ABCA1[p.Q1038X/ p.N1800H]. Login to comment 150 ABCA1 p.Cys1477Arg ABCA1 p.Asn1800His ABCA1 p.Gln1038* Male/female TC HDL-c apoA-I apoA-II LDL-c apoB TG apoA-I mutation carriers Unaffected (n=3) 1/2 179±27 45±3 163±13 30±1 131±22 97±15 97±25 Heterozygotes (n=3) 1/2 141±12* 20±14* 87±38* 19±6* 113±5 85±6 97±45 ABCA1 mutation carriers Unaffected (n=8) 4/4 171±56 57±15 160±29 30±4 111±23 84±12 85±20 Heterozygotes (n=6) 3/3 179±64 37±7** 124±12** 28±2 129±35 98±22 90±44 Compound heterozygote 1c (n=1) 1/0 54 6 4 2 44 75 138 Compound heterozygote 2d (n=1) 0/1 220 3 7 ndb 173 192 387 Homozygote (n=1) 0/1 63 0.8 nd nd 61 81 87 LCAT mutation carriers Unaffected (n=7) 5/2 199±32 49±13 166±19 31±2 134±28 100±20 123±58 Heterozygotes (n=12) 8/4 166±47 32±11** 122±27*** 26±5* 122±38 97±28 115±49 Compound heterozygotes (n=3) 0/3 140±24* 5±1*** 48±8*** 3.8±0.3*** 118±17 102±27 244±103* Homozygote (n=1) 1/0 107 3 58 4 77 118 279 a Values presented as mean±SD (mg/dl); b nd, not detectable; c ABCA1[p.C1477R/IVS25+1GNC]; d ABCA1[p.Q1038X/ p.N1800H]. Login to comment 159 ABCA1 p.Cys1477Arg ABCA1 p.Leu1056Pro HDL from heterozygotes for ABCA1 mutations (p.C1477R, p.L1056P), incubated in the absence or presence of LDL, increased the fluorescence signal by 39% (p=0.043) and 41% (p=0.029), respectively, compared to controls (Fig. 2A). Login to comment 160 ABCA1 p.Cys1477Arg ABCA1 p.Leu1056Pro A previous study has shown that heterozygotes for ABCA1 mutation p.C1477R, but not for ABCA1 mutation p.L1056P, have increased CAD compared to unaffected family members [24,25]. Login to comment 161 ABCA1 p.Cys1477Arg ABCA1 p.Leu1056Pro These observations may be related to the current finding (although the number of analyzed samples is small) that HDL from heterozygotes for ABCA1 mutation p.C1477R was more oxidized and contained higher MDA levels compared to HDL from heterozygotes for ABCA1 mutation p. L1056P (Fig. 2A, B). Login to comment 162 ABCA1 p.Cys1477Arg ABCA1 p.Leu1056Pro HDL from heterozygotes for ABCA1 mutations (p.C1477R, p.L1056P), incubated in the absence or presence of LDL, increased the fluorescence signal by 39% (p=0.043) and 41% (p=0.029), respectively, compared to controls (Fig. 2A). Login to comment 163 ABCA1 p.Cys1477Arg ABCA1 p.Cys1477Arg ABCA1 p.Cys1477Arg ABCA1 p.Cys1477Arg ABCA1 p.Cys1477Arg ABCA1 p.Asn1800His ABCA1 p.Asn1800His ABCA1 p.Gln1038* ABCA1 p.Gln1038* ABCA1 p.Leu1056Pro ABCA1 p.Leu1056Pro ABCA1 p.Leu1056Pro A previous study has shown that heterozygotes for ABCA1 mutation p.C1477R, but not for ABCA1 mutation p.L1056P, have increased CAD compared to unaffected family members [24,25]. Login to comment 164 ABCA1 p.Cys1477Arg ABCA1 p.Leu1056Pro These observations may be related to the current finding (although the number of analyzed samples is small) that HDL from heterozygotes for ABCA1 mutation p.C1477R was more oxidized and contained higher MDA levels compared to HDL from heterozygotes for ABCA1 mutation p. L1056P (Fig. 2A, B). Login to comment 166 ABCA1 p.Cys1477Arg ABCA1 p.Cys1477Arg ABCA1 p.Cys1477Arg ABCA1 p.Cys1477Arg ABCA1 p.Asn1800His ABCA1 p.Asn1800His ABCA1 p.Gln1038* ABCA1 p.Gln1038* ABCA1 p.Leu1056Pro ABCA1 p.Leu1056Pro Compound heterozygotes for ABCA1 mutations * * 0 10000 20000 30000 40000 50000 60000 70000 L1056P L1056P C1477R C1477R ** ** C1477R/ IVS25+1G>C Q1038X/ N1800H C1477R/ IVS25+1G>C Q1038X/ N1800H 0.0 2.5 5.0 7.5 10.0 SAA/HDL-c(RLU) ** 0 10 20 30 40 *** 0 1 2 3 PAF-AHactivity (nmolCE/h) A B C D * ** HDL C HDL Het HDL Com HDL Hom HDL C HDL Het HDL Com HDL Hom HDL C HDL Het HDL Com HDL Hom DCF LDL HDL C HDL HetHDL C +LDL HDL Het + LDL HDL Com HDL Com +LDL Fluoresence(AU) MDA/HDL-c(RLU) Fig. 2. Login to comment 173 ABCA1 p.Cys1477Arg ABCA1 p.Leu1056Pro p.C1477R/ IVS25+1GNC and a homozygote for ABCA1 mutation p.L1056P presented with CAD [24,25]. Login to comment 174 ABCA1 p.Asn1800His ABCA1 p.Gln1038* A compound heterozygote for ABCA1 mutations p.Q1038X/ p.N1800H did not present with CAD [25]. Login to comment 176 ABCA1 p.Cys1477Arg ABCA1 p.Leu1056Pro p.C1477R/ IVS25+1GNC and a homozygote for ABCA1 mutation p.L1056P presented with CAD [24,25]. Login to comment 177 ABCA1 p.Asn1800His ABCA1 p.Gln1038* A compound heterozygote for ABCA1 mutations p.Q1038X/ p.N1800H did not present with CAD [25]. Login to comment 178 ABCA1 p.Leu1056Pro The HDL from the ABCA1 homozygote for mutation p.L1056P was extremely low and could not be tested for its antioxidant/anti-inflammatory properties by the DCF assay. Login to comment 181 ABCA1 p.Leu1056Pro The HDL from the ABCA1 homozygote for mutation p.L1056P was extremely low and could not be tested for its antioxidant/anti-inflammatory properties by the DCF assay. Login to comment 184 ABCA1 p.Asn1800His Loss of large b1;1 subpopulation and decrease in b1;2 apoA-I-containingHDL subpopulations has also been reported for other heterozygotes for ABCA1 gene defects (from two kindreds carrying ABCA1 mutation p.N1800H or variant aa217 to stop), while homozygotes (Tangier disease patients) were reported to only have pre-b2;1 apoA-I-containing HDL subpopulations [32]. Login to comment 187 ABCA1 p.Asn1800His Loss of large α1 subpopulation and decrease in α2 apoA-I-containingHDL subpopulations has also been reported for other heterozygotes for ABCA1 gene defects (from two kindreds carrying ABCA1 mutation p.N1800H or variant aa217 to stop), while homozygotes (Tangier disease patients) were reported to only have pre-β1 apoA-I-containing HDL subpopulations [32]. Login to comment