Analysis of SAA1 gene polymorphisms in the Greek population: rheumatoid arthritis and FMF patients relative to normal controls. Homogeneous distribution and low incidence of AA amyloidosis

Objective. To address whether or not the rarity of amyloidosis in Greek patients with rheumatoid arthritis (RA) is related to specific alleles of single nucleotide polymorphisms (SNPs) in the 5'-flanking region and the exon 3 of the SSA1 gene. Methods. The genotypes of the - 13T/C SNP in the 5'-flanking region of the SAA1 gene and the two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined in 88 Greek patients with RA, 14 patients with familial Mediterranean fever (IMF) and 110 healthy controls. Linkage disequilibrium and haplotype frequencies involving - 13T/C, 2995C/T and 3010C/T in these populations were tested and estimated, respectively. Results. The genotypic distribution and allelic frequencies were similar in all groups tested. SNPs 2995 and 3010 were in linkage disequilibrium for all study populations (p = 0.05). Two major haplotypes presented in all patients with RA and FMF and controls: - 13C; 2995T; 3010C (- 13C; alpha) and - 13C; 2995C; 3010T (- 13C; beta). The - 13T allele was linked with the 7 haplotype in Greek patients with RA and controls. The frequency of the - 13T allele was found to be very rare in all groups tested. Conclusions. In conclusion, the rarity of the putative amyloidogenic - 13T allele in Greek populations may be related to low prevalence of AA amyloidosis development in Greek RA patients

XbaI GLUT1 gene polymorphism and the risk of type 2 diabetes with nephropathy

Altered expression of the facilitated glucose transporter GLUT1 affects pathways implicated in the pathogenesis of diabetic nephropathy. There is indication that variation of GLUT1 gene (SLC2A1) contributes to development of microangiopathy in diabetes mellitus type 2 (DM) patients. A genetic association study involving Caucasians was carried out to investigate the role of XbaI polymorphism in the GLUT1 gene in diabetic nephropathy (DN). Study population (n - 240) consisted of 148 unrelated patients with DM (92 cases with diabetic nephropathy (DN)), and of 92 matched healthy control subjects. Diabetic nephropathy was defined as persistent albuminuria (> 300 mg/24 h) and/or renal failure, in the absence of non-diabetes induced renal disease. The analysis showed that the risk of developing DM and DN in XbaI(-) carriers, when healthy individuals were considered as controls, was two-fold: odds ratio (OR) 2.08 [95% confidence interval (1.14-3.79)]. However, there was no evidence of association between XbaI(-) and DN when patients with DM and without DN were considered as controls: OR = 1.12 (0.55-2.26). Thus, the GLUT1 XbaI(-) allele is associated with DM, and possibly with a more severe form of the disease that can lead to development of DN

Genetic variation within IL18 is associated with insulin levels, insulin resistance and postprandial measures☆

BACKGROUND AND AIMS: IL-18 expression is up-regulated in atherosclerotic plaques, and higher levels are seen in obese and Type 2 Diabetic individuals. More recently, a possible role for IL-18 in glucose and energy homeostasis has been suggested. METHODS AND RESULTS: We investigated variation within the IL18 gene and its association with measures of obesity and the metabolic syndrome. Five IL18 tagging single nucleotide polymorphisms (rs1946519, rs2043055, rs549908, rs360729, rs3882891) were selected and genotyped in the Gene-Diet Attica Investigation on childhood obesity (GENDAI) (age range 10-14 yrs); in young European men in the second European Atherosclerosis Research offspring Study (EARSII), an offspring study (age range 18-28 yrs) and in a group of healthy women from the Greek Obese Women study (GrOW) (age range 18-74 yrs). Six common haplotypes were observed. In GrOW, Hap6 (Frequency-2.6%) was associated with higher insulin levels (p<0.0001), estimates of HOMA(-Insulin Resistance) (p<0.0001) and HOMA(-β-cell) (p<0.0001) compared to the common haplotype Hap1 (Frequency-33.2%). In EARSII, rs2043055 was associated with peak and area under the curve triglycerides (p=0.001 and p=0.002, respectively) after an oral fat tolerance test in 'cases' but not 'controls'. None of the haplotypes were associated with measures of body fatness in any of the studies. CONCLUSION: Association of IL18 variation with insulin levels and estimates of insulin resistance were only observed in our adult study, suggesting that the effects of IL-18 are only associated with increasing age. Taken together with the association of IL18 variants with post-prandial measures, this provides support for IL-18 as a metabolic factor