Genetic analysis of rheumatic fever among Egyptian families: consanguinity pattern, segregation analysis and blood group association

ABSTRACT

To assess genetic background of Rheumatic Fever [RF] among Egyptian families and to test for association to blood group allelic phenotypes. This study was done on 30 Egyptian rheumatic families of which 10 were mutiplex; enrolled from Pediatric Cardiology Clinic, Mansoura University Hospital. Subjects included 30 probands and 1142 relatives of different degrees; they were classified clinically into 46 cases with RF, 136 subjects with recurrent Upper Respiratory Infection [URTI] and/or arthralgia and the remainders were irrelevant. Diagnosis of RF was based on Jones criteria. Pedigree analysis with stress on consanguinity, positive family history of RF and definite recurrent URTI. Nine blood group systems were analyzed for probands including; ABO, Rh, MNS, Kell, Lutheran, Lewis, Kidd, Duffy, P1 and individual secretor status. In rheumatic families consanguinity and inbreeding were higher than control [53.3%, 0.015]. Segregation analysis suggested multifactorial inheritance for RF with mean heritability [30%] whereas recurrent URTI followed recessive inheritance. Some alleles and phenotypes were of higher incidence in probands compared to control; alleles se [non-secretor], D, Jka+ and phenotypes Lu [a-b-], Le [a-b-] and Fy [a-b-] were of higher frequency, whereas alleles Se [secretor], A, B, Kp a+, Lu b+, Le b+, Fy a+, Fy b+ and phenotypes Fy [a+ b+], Sese or SeSe [secretor] were less frequent. Based on the inherited susceptibility to respiratory infection, RF is a genetic disease with multifactorial inheritance. Blood group systems on chromosome 19 could mark hot spots for further linkage and gene mapping