Inducible nitric oxide synthase (NOS2) promoter CCTTT repeat polymorphism: relationship to in vivo nitric oxide production/NOS activity in an asymptomatic malaria-endemic population.
Polymorphisms in the inducible nitric oxide synthase gene (NOS2) promoter have been associated with clinical outcome from malaria. These include a CCTTT repeat (CCTTTn) 2.5 kilobases upstream from the NOS2 transcription start site, and two single nucleotide substitutions: G-->C at position -954 (G-954C), and C-->T at position -1173 (C-1173T). Although hypothesized to influence NO production in vivo, the functional relevance of (CCTTT)n and G-954C is uncertain because disease association studies have yielded inconsistent results. This study found no association between CCTTT repeat number and levels of plasma NO metabolites or peripheral blood mononuclear cell NOS activity in a cohort of asymptomatic malaria-exposed coastal Papua New Guineans 1-60 years old. This suggests that (CCTTT)n does not independently influence NOS2 transcription in vivo. Neither the G-954C nor the C-1173T polymorphisms were identified in this population, indicating the variability and complexity of selection for NOS2 promoter polymorphisms in different malaria-endemic populations.
Boutlis
Craig S
CS
International Health Program, Infectious Diseases Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
Hobbs
Maurine R
MR
Marsh
Robyn L
RL
Misukonis
Mary A
MA
Tkachuk
Ariana N
AN
Lagog
Moses
M
Booth
Jennifer
J
Granger
Donald L
DL
Bockarie
Moses J
MJ
Mgone
Charles S
CS
Levesque
Marc C
MC
Weinberg
J Brice
JB
Anstey
Nicholas M
NM
D005260:Female; D006801:Humans; D008297:Male; D019353:Endemic Diseases; D020022:Genetic Predisposition to Disease; D008288:Malaria / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010219:Papua New Guinea / Q000453:epidemiology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496319:NOS2 protein, human