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International Angiology 2002 December;21(4):379-83


lingua: Inglese

Association of the HLA antigens with early atheromatosis in subjects with type 2 diabetes mellitus

Diamantopoulos E. J. 1, Andreadis E. A. 1, Kakou M. G. 1, Vassilopoulos C. V. 1, Vlachonikolis I. G. 2, Giannakopoulos N. A. 1, Tarassi K. E. 3, Papasteriades C. A. 3, Nicolaides A. N. 4

1 4th Department of Internal Medicine, “Evangelismos” State General Hospital, Athens, Greece 2 Department of Medical Statistics, Medical School, University of Crete, Crete, Greece 3 Histocompatibility Department, “Evangelismos” State General Hospital, Athens, Greece 4 The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus and Department of Vascular Surgery, Imperial College, London, UK


Background. Inflammation plays an impor­tant role in the path­o­gen­e­sis of ath­ero­scler­o­sis. The major his­to­com­pat­ibil­ity com­plex, as ­expressed by the human leu­ko­cyte anti­gens (HLA) is con­sid­ered to reg­u­late the ­immune ­response. The aim of this study was to inves­ti­gate the asso­ci­a­tion of the HLA anti­gens with vas­cu­lar remod­el­ing esti­mat­ed by the carot­id inti­ma-media thick­ness (IMT) in sub­jects with type 2 dia­betes mel­lit­us (DM).
Methods. We eval­u­at­ed 197 ­patients with type 2 DM, 80 males and 117 ­females, mean age 61.8±7.8 years, with­ no his­to­ry of car­di­o­vas­cu­lar ­events. The pres­ence of other major car­di­o­vas­cu­lar risk fac­tors was record­ed. The cur­rent­ly iden­ti­fied HLA class I (-A, -B, -Cw) and class II (DR, -DQ) anti­gens were stud­ied by a clas­si­cal 2 step micro­lym­pho­cy­to­tox­ic tech­nique in periph­er­al blood T and B lym­pho­cytes. Measurements of the IMT were per­formed in the right and left com­mon carot­id arter­ies, 15-20 mm prox­i­mal to the dil­a­ta­tion of the carot­id bulb in an end-dia­stol­ic “fro­zen” and mag­ni­fied B-mode ultra­son­o­graph­ic image. Glycosylated hemo­glo­bin A1c (HbA1c) and C-reac­tive pro­tein (CRP) were also meas­ured. The ­results are pre­sent­ed as mean ±1 stan­dard devi­a­tion.
Results. Regarding the HLA phe­no­types in the final anal­y­sis we test­ed a total of 24 HLA anti­gens that exhib­it­ed a fre­quen­cy of at least 5% in our dia­bet­ic pop­u­la­tion. Only HLA A3 was found to be sig­nif­i­cant­ly asso­ciat­ed with the carot­id IMT. Forty-nine (24.9%) dia­bet­ics were HLA A3 pos­i­tive (group A), while 148 (75.1%) were HLA A3 neg­a­tive (group B) and had mean IMT of 0.89±0.16 mm and 0.98±0.21 mm, respec­tive­ly (p<0.01). Also the two ­groups dif­fered sig­nif­i­cant­ly in ­respect to CRP, with group A exhib­it­ing lower serum lev­els (1.1±0.4 mg/dl vs 2.6±0.7 mg/dl for group A and B, respec­tive­ly, p<0.05). However, no dif­fer­enc­es were ­observed ­between the two ­groups as far as blood glu­cose con­trol, arte­ri­al hyper­ten­sion and dys­lip­i­dae­mia were con­cerned.
Conclusions. Human leu­ko­cyte anti­gen A3 is asso­ciat­ed with less vas­cu­lar dam­age, as ­expressed by carot­id wall thick­ness, in sub­jects with type 2 DM. These sub­jects may be char­ac­ter­ized by a mild­er inflam­ma­to­ry ­response, as shown by the lower serum lev­els of CRP.

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