Serologic screening and genetic testing among brazilian patients with celiac disease and their first degree relatives

Abstract

-Context -Celiac disease susceptibility has been shown to be associated with the HLA alleles DQA1*0501 and DQB1*0201 (together encoding the DQ2 heterodimer) that are present in practically all celiac disease patients. The DQ8 heterodimer (coded by DQA1*03-DQB1*0302), which is carried on a DRB1*04 (DR4) haplotype, is commonly encoded for by the few celiacs who do not carry the DQ2 heterodimer. Only a few celiac disease patients have been reported without these known risk alleles. Objective -To assess the prevalence of celiac disease in a group of first degree relatives of celiac patients, and the frequency of HLA predisposing alleles both in the group of celiac patients and in their first degree relatives, identifying those first degree relatives who would need further screening for celiac disease. Methods -Ninety celiac disease patients and 207 first degree relatives underwent serologic screening for celiac disease (endomysial and transglutaminase antibodies) followed by intestinal biopsy in positive patients. The HLA-DQA1*0501, DQB1*0201 and DRB1*04 frequencies of celiac patients and their first degree relatives were determined utilizing the PCR method.Results -All the celiac disease patients (n = 90) with the exception of one (1.1%) carried at least one of the alleles investigated. Altogether 11 (5.3%) of the investigated first degree relatives did not carry any of the alleles studied. Fourteen (6.7%) new cases of celiac disease were found among the 207 celiac disease patients first degree relatives. Conclusions -Considering the cost-benefit of the HLA typing of all the first degree relatives of celiac patients, their HLA status should be decided on an individual basis, taking account of their profile and preferences, and the existence of other medical conditions.

Prevalence of Genetic Susceptibility for Celiac Disease in Blood Donors in São Paulo, Brazil

“…Castro-Antunes et al found genetic predisposition in 78.6% of the patients' relatives in the North East region (4) , and a study performed in the Center West region by Martins et al, described the DQ2 allele in 42% of the relatives, being DQ2 associated to DRB1*04 in 13% and DRB1*04 alone in 4.6% of the individuals (19) . However, since the studies were performed in relatives, it was not possible to detect the real genetic predisposition for CD in the Brazilian general population.…”

Risk of Celiac Disease in the First- and Second-Degree Relatives of Patients With Celiac Disease: A Systematic Review and Meta-Analysis

“…Forty-eight studies were included in this part of analysis as they reported serological prevalence among FDRs with one index case of CD ( 9,(11)(12)(13)(14)(30)(31)(32)(33)(34)(35)(36)39,(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(52)(53)(54)(55)(56)(57)(58)(59)(60)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78). Overall, of 14,225 FDRs screened using AEA and/or anti-tTG Ab, 1,016 FDRs were seropositive ( 9,(11)…”

“…Of the 41 studies, 24 studies further mentioned prevalence of CD according to the relationship of FDRs with the index patient with CD ( 9,(12)(13)(14)(32)(33)(34)36,37,41,42,44,46,47,49,50,(52)(53)(54)(55)57,59,60,76 ). Of 2,780 siblings in these studies, 254 had CD, therefore pooled prevalence of CD in siblings was 8.9% (95% CI 6.6, 11.2%).…”

“…Heterogeneity in these subgroups was reduced to 39.8% among parents, 66.7% among off springs, and 71.2% among siblings. Almeida (2008) Cataldo (2003) Uenishi (2014) Bonamico (1996) Kocksis (2013) Maki (1991) Chomeili (2011) Kolek (2001) Dolinsek (2004) Oliveira (2012) Srivastava (2010) Dogan (2012) Bardella (2007) Gautam (2006) Rostami (1999) Piccini (2012) Goel (2007) Petaros (2002) Dezi ( daughter, and son ( 9,(12)(13)(14)(32)(33)(34)36,37,41,42,44,46,47,49,50,(52)(53)(54)(55)57,59,60,76 ). Th e pooled prevalence of CD in each of the FDRs with specifi c relationships to the index patient is summarized in Table 3 .…”

Major histocompatibility complex class I chain related gene‐A microsatellite polymorphism shows secondary association with type 1 diabetes and celiac disease in North Indians

“…In Caucasians, HLA‐DRB1*04‐DQA1*03:01‐DQB1*03:02 (DR4‐DQ8) and DRB1*03‐DQA1*05:01‐DQB1*02:01 (DR3‐DQ2) are positively associated with T1D and referred to as ‘high risk’ class II haplotypes, whereas HLA‐DRB1*15‐DQA1*01:02‐DQB1*06:02 (DR15‐DQ6) is negatively associated and hence protective . More than 90% of patients with CD express the HLA‐DQ2 heterodimer, encoded by the high risk‐associated haplotype DQA1*05:01‐ DQB1*02 in cis position in HLA‐DR3 patients or in trans position in HLA‐DR5/DR7 heterozygous patients . In the North Indian population, on the other hand, the greatest risk is conferred by the DR3‐DQ2 haplotypes with almost no association with DR4‐DQ8, both in T1D as well as active CD .…”