Affiliations: Department of Medical Laboratory Sciences, Faculty of
Allied Health Sciences, Kuwait University, Hawally, Kuwait
Note: [] Corresponding author: Suad AlFadhli, Department of Medical
Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University,
Kuwait, Kuwait PO Box 31470 Sulaibekhat, Kuwait. Tel.: +965 6000 2088; Fax:
+965 2498 3835; E-mail: [email protected], [email protected]
Abstract: The purpose of this study was to analyse the effect of the T-786C
polymorphism and intron 4 27 bp variable number tandem repeat(VNTR) eNOS
markers for their potential association with Systemic Lupus Erythematosus(SLE),
Hashimotos thyroiditis(HT) and Rheumatoid arthritis(RA) as well as to explore
their effect on eNOS mRNA expression and nitrate production(NOx). Kuwaitis
(n=383) matched by age, gender and ethnicity were genotyped by
fluorescent-labelled-restriction fragment length polymorphism (RFLP) and
fragment analysis. Expression of eNOS mRNA was analysed using RT-PCR and sera
from subjects were screened for NOx using ELISA. Analysis of the allelic
frequency revealed a significant association of the 4b allele with
susceptibility to SLE (p=0.0092, OR=1.76). The 4bb genotype was found to be
associated with SLE (p=0.0076, OR=1.97) and HT (p=0.05, OR=1.81). Allelic and
genotypic distribution did not differ between RA patients and healthy control
subjects. The 4bb genotype resulted in reduced expression of eNOS mRNA in SLE,
RA and HT, but only the reduction in HT was significant (p=0.05). The 4ab
genotype revealed a significant association with increased eNOS expression in
HT (p=0.03) and RA (p=0.014) patients, and elevated NOx levels were detected in
the autoimmune disease cohorts (p< 0.05) when compared to healthy control
subjects. The T-786C SNP failed to show a significant association (p> 0.05)
with SLE, HT, and RA patients. This study is the first to reveal a significant
association between the 4bb genotype of the 27 bp VNTR and susceptibility to
HT. The expression of eNOS is related to the number of 27 bp repeats, with
heterozygous 4bb repeats showing a decrease in eNOS expression. eNOS –
endothelial nitric oxide synthase.
