Association of HLA-DR/DQ polymorphisms with schizophrenia in Tunisian patients

Abstract

BACKGROUND AND OBJECTIVESThe hypothesis that human leukocyte antigens (HLAs) confer susceptibility to schizophrenic disorders has been tested by studying linkage and association in family samples. Our goal was to evaluate the role of HLA in the risk of developing schizophrenia in a Tunisian population.DESIGN AND SETTINGSBlood samples for this case-control study were collected from patients of the Department of Psychiatry at the Military Hospital of Tunisia between July 2012 and May 2013.METHODSA total of 140 patients with schizophrenia were recruited for genetic analysis. Controls included 100 persons matched for age, sex, and risk factors. Participants were tested for HLA class II alleles. HLA-DRB1 and HLA-DQB1 alleles were genotyped using polymerase chain reaction sequence-specific primers.RESULTSThis study indicates that the alleles most responsible for disease susceptibility are DRB1*03 (P<10−3) and DQB1*02 (P<10−3) (P denotes probability values). The most protective alleles are DRB1*13 (P=.013) and DQB1*05 (P<10−3). Further results revealed that DRB1*0301/DQB1*0201(P<10−3), DRB1*0401/DQB1*0301 (P<10−3) and DRB1*1101/DQB1*0301 (P<10−3) are haplotypes most conducive to disease susceptibility.CONCLUSIONThe present findings support an association between schizophrenia and the HLA-DR-DQ locus among a Tunisian population. To our knowledge, this is the first study performed to analyze the association of HLA DRB1/DQB1 alleles on schizophrenia susceptibility in Tunisia.

HLA DRB1*03 as a possible common etiology of schizophrenia, Graves’ disease, and type 2 diabetes

“…Furthermore, the HLA-DRB1 gene has been a focus in investigating the HLA association with schizophrenia [ 17 ]. A strong positive association between HLA-DRB1*03 and HLA DQB1*02 alleles and schizophrenia has widely been reported in the Saudi and Tunisian populations [ 18 , 19 ].…”

Association of HLA class II alleles with suicidal behavior in a Transylvanian population

“…Based on our risk ratio values, other alleles presumably susceptible to alleviate the risk of suicidal behavior are HLA-DQB1*08, *01 or *14 (RR of .6-.7), in contrast to HLA-DQB1*12 (RR 1.67). In accordance with these data, a Tunisian study found the DQB1*02 allele to be the most susceptible and DQB1*05 the most protective in schizophrenia patients [32]. On the other hand, an American study on a huge cohort of mainly Caucasian deceased organ donors [33] which associated intentional violent death with 21 HLA-DR and 10 HLA-DQ alleles found both DQB1*02 and DQB1*05 to be significantly associated with increased risks for violent death.…”

Association of HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 alleles at amino acid level in individuals with schizophrenia: A study from South India

“…Gender‐specific associations revealed that DRB1*10:01:01 and DQB1*05:01:01 were positively associated while DQB1*03:02:01 was negatively associated in female subjects with schizophrenia. According to earlier studies, DQB1*05 has been reported to be a protective allele in Tunisians (Sayeh et al., 2014) while DQB1*03 as a susceptible allele in Singapore Chinese population (Nimgaonkar, Rudert, Zhang, TsoiWF, & Saha, 1995), though they were not gender specific. In the present study, DQB1*06:01:01 was found to be a susceptible allele among male subjects with schizophrenia, in contrast to a previous report from Singapore Chinese population where the allele has been reported to be a protective allele (Nimgaonkar et al, 1995).…”

“…Haplotype analysis revealed a significant protective association for the haplotypes DRB1*04:03:01~DQB1*03:02:01. However, this haplotype was reported as a susceptible haplotype in Tunisian population (Sayeh et al., 2014). The present study has also brought out that A*01:01:01~B*37:01:01~C*06:02:01~DRB1*10:01:01~DQB1*05:01:01 is the predominant haplotype in schizophrenia population when compared to healthy controls.…”

“…DRB1*03 was found to be a risk factor for schizophrenia in Saudi Arabian and Tunisian population (Akaho et al., 2000; Kadasah, Arfin, & Tariq, 2011; Ozcan, 2006; Sayeh et al., 2014). A significantly higher rate of HLA‐DR1 (DRB1*0101) has been reported in Japanese patients with schizophrenia than in normal subjects (Miyanga, Machiyama, & Juji, 1984; Sasaki et al., 1994, 1999).…”