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SummaryCommon variable immunodeficiency (CVID) is a heterogeneous group of primary immunodeficiency diseases. Cytokine production could be affected in CVID patients, whereas its alteration could be due to genetic polymorphisms within coding and promoter regions of the cytokine genes. This study was performed to analyse the proinflammatory cytokine single nucleotide polymorphisms in CVID. The allele and genotype frequencies of a number polymorphic genes coding tumour necrosis factor (TNF)-a, interleukin (IL)-1a, IL-1b, IL-1R, IL-1RA and IL-6 were investigated and compared between two groups of CVID patients and controls. The IL-6 GA genotype at position nt565 was significantly over-represented in the patient group (P < 0·001), while the IL-6 GG genotype at position -174 (P = 0·006) and the GG genotype at position nt565 (P < 0·001) were significantly lower than controls. The TNF-a AG genotype at position -308 in the patient group was increased significantly in comparison with controls (P = 0·027), but the GG genotype at the same position was significantly decreased (P = 0·011). IL-6 CA and GA haplotypes were the most frequent haplotypes in the patients (P < 0·005), whereas TNF-a GA (P = 0·002) and IL-6 GG (P < 0·001) haplotypes were decreased significantly in the patients in comparison with controls. Cytokine single nucleotide polymorphisms could have a role in pathophysiology of CVID. High production of TNF-a is expected in some CVID patients based on the frequency of genotypes/haplotypes of these cytokine gene polymorphisms.

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We have previously shown that angiotensin-converting enzyme (ACE) gene D allele is an independent risk factor for early onset coronary artery disease (CAD). Little is known about the concomitant presence of the ACE gene D allele and paraoxonase (PON1) codon 192 arginine (Arg) on the severity of CAD. Regarding the high rate of CAD among Iranians the aim of present study was to examine the hypothesis of synergistic effects between ACE-D and PON1-Arg alleles on predisposition and the severity of CAD in our population. The PON1 192 and ACE insertion/deletion (I/D) genotypes were detected by PCR-RFLP and PCR, respectively in 414 individuals undergoing their first coronary angiography. Patients were placed into one of two groups: CAD and control without CAD or diabetes. We mentioned the synergistic effects of both genes and not ACE gene alone is a risk factor for CAD. We found that PON1 Arg 192 and ACE D allele act synergistically to increase the risk of CAD (OR 1.3, P = 0.044). Our results showed a significant correlation between the possession of both PON1 192 Arg and the ACE D allele and the extent of CAD in CAD patients and CAD subjects without diabetes, represented by the increased frequency of three-vessel disease with OR 2.7, P = 0.046; χ(2) = 4, P = 0.046 and OR 2.4, P = 0.051; χ(2) = 3.8, P = 0.051, respectively. We found that PON1 Arg 192 and ACE D alleles act synergistically to increase the risk of CAD in CAD patients and CAD subjects without diabetes from west of Iran, who have high frequency of three-vessel disease. Our data suggest that PON1 192 Arg and the ACE D allele in combination with each other can be important independent risk factor for severity of CAD in patients carrying both PON1 192 Arg and the ACE D allele in a west population of Iran.