Beta2-glycoprotein I gene polymorphisms Val247Leu and Trp316Ser in Spanish patients with primary antiphospholipid syndrome.
The significance of beta2-glycoprotein I (β2GPI) polymorphisms in the production of anti-β2GPI and other antiphospholipid autoantibodies (aPL) and in the pathogenesis of primary antiphospholipid syndrome (PAPS) is not well understood. We performed a study comparing the distribution of polymorphisms at codons 247 (Val247Leu) and 316 (Trp316Ser) of the β2GPI gene in a Caucasian Spanish population of PAPS patients and healthy controls, and then making correlations with the development of anti-β2GPI antibodies and other aPL and associated clinical manifestations. A total of 57 PAPS patients and 100 control subjects were included. In the analysis of Val247Leu polymorphism, alleles (V and L) and genotypes (V/V, V/L, L/L) were similarly distributed in PAPS patients and controls (P = 0.66 and P = 0.22, respectively). Regarding Trp316Ser polymorphism, we found a higher percentage of patients with respect to controls expressing S allele (11.4 vs. 5%, P = 0.02) and T/S genotype (22.8 vs. 10%, P = 0.02). However, when we compared T/T and T/S genotypes in PAPS patients, we found no differences regarding generation of anti-β2GPI, other aPL and clinical manifestations favoring any genotype. Our findings suggest that among Spanish Caucasians, polymorphisms at codon 247 (Val247Leu) do not seem to influence PAPS pathogenesis. On the contrary, polymorphisms at codon 316 (Trp316Ser), by means of an increased S allele and T/S genotype presence in Spanish Caucasian patients, might play a role in the pathogenic development of PAPS, although mechanism would not involve an increased production of anti-β2GPI and other aPL.
Autoimmune Diseases Research Laboratory, Vall d'Hebrón University Hospital Research Institute, Universitat Autonoma de Barcelona, Passeig de Vall d'Hebron 119-129, 08035 Barcelona, Spain. jpardosgea@yahoo.es
J
J
Pardos-Gea
J
J
Castro-Marrero
J
J
Cortés-Hernández
E
E
Balada
A
A
Pedrosa
M
M
Vilardell-Tarrés
J
J
Ordi-Ros
D000328:Adult; D000483:Alleles; D017152:Antibodies, Antiphospholipid / Q000235:genetics / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013030:Spain; D044465:White People / Q000235:genetics; D053482:beta 2-Glycoprotein I / Q000235:genetics*
D017152:Antibodies, Antiphospholipid; D053482:beta 2-Glycoprotein I
Clin Exp Immunol. 1987 Apr;68(1):215-22
3652514
Hum Genet. 1993 May;91(4):401-2
8099061
J Thromb Haemost. 2006 Feb;4(2):295-306
16420554
Lancet. 1993 Aug 7;342(8867):341-4
8101587
Arthritis Rheum. 2005 Jan;52(1):212-8
15641049
Hum Genet. 1997 Jul;100(1):57-62
9225969
CMAJ. 2003 Jun 24;168(13):1675-82
12821621
Lupus. 2006;15(4):218-22
16686261
Blood. 1986 Oct;68(4):869-74
3092888
Arthritis Rheum. 1999 Jun;42(6):1189-93
10366111
Br J Haematol. 1978 Sep;40(1):143-51
568479
Clin Rheumatol. 2007 Mar;26(3):302-7
16724168
Eur J Biochem. 1999 Jan;259(1-2):435-40
9914524
Ann Hum Genet. 2006 Jan;70(Pt 1):1-11
16441253
Brain Nerve. 2008 Nov;60(11):1333-8
19069167
Hum Immunol. 2000 Apr;61(4):366-77
10715514
J Exp Med. 1994 Feb 1;179(2):457-62
7507506
Stroke. 1997 Sep;28(9):1660-5
9303006
Thromb Haemost. 1995 Oct;74(4):1185-90
8560433
Arthritis Rheum. 2003 Feb;48(2):471-4
12571857
Am J Clin Pathol. 1990 Oct;94(4):476-84
2220676
J Immunol. 1996 Oct 15;157(8):3744-51
8871678
Blood. 2001 Sep 15;98(6):1889-96
11535526
Arthritis Rheum. 1999 Aug;42(8):1655-61
10446865
Ann N Y Acad Sci. 2009 Sep;1173:509-14
19758193
Lupus. 1999;8(9):742-50
10602447
Blood. 1985 Nov;66(5):1086-91
4052628
Rheumatology (Oxford). 1999 Aug;38(8):721-3
10501418
Br J Haematol. 2003 Mar;120(6):1066-72
12648080
J Immunol. 1995 Jan 15;154(2):954-60
7814895