title: Variants of endothelial nitric oxide synthase gene are associated with components of metabolic syndrome in an Arab population.
abstract: Genetics plays a crucial role in the development of metabolic syndrome (MetS).  Here we examined the association between endothelial nitric oxide synthase (eNOS) gene polymorphisms and MetS in a Saudi Arabian cohort to extend the understanding of the genetic basis of MetS in diverse ethnic populations.  Anthropometric, clinical and biochemical parameters as well as genotyping for 894G>T, -786T>C variants of eNOS gene by PCR-RFLP and 4a/b by direct PCR were performed in 886 Saudi Arabians (477 MetS and 409 Non-MetS).  The genotype distribution (TT, p=0.001; TC, p=0.001; TC+CC, p=0.001) and allele (T, p=0.007; C, p=0.007) frequency of the -786T>C SNP were significantly different between Non-MetS and MetS subjects which remained significant after Bonferroni correction. Moreover: 1) the GT and GT+TT genotypes of the 894G>T SNP were associated with elevated blood pressure (p=0.017, and p=0.022, respectively); 2) the ab variant of 4a/b polymorphism was associated with decreased HDL levels (p= 0.044); and 3) the TC+CC genotype and C allele of the -786T>C SNP were associated with increased fasting glucose levels (p=0.039, and p=0.028, respectively).  Also, G-a-C was identified as the risk haplotype for MetS susceptibility (p=0.034).  The results suggest a significant association of 894G>T, 4a/b and -786T>C polymorphisms with MetS and its components is present in an Arab population.  A genetic predisposition to develop abnormal metabolic phenotypes, consistent with an increased prevalence of metabolic phenotypes can be detected in this ethnic group.
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. alkharfy@ksu.edu.sa
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Alkharfy
authors.forename: Nasser M
authors.initials: NM
authors.lastname: Al-Daghri
authors.forename: Omar S
authors.initials: OS
authors.lastname: Al-Attas
authors.forename: Majed S
authors.initials: MS
authors.lastname: Alokail
authors.forename: Abdul Khader
authors.initials: AK
authors.lastname: Mohammed
authors.forename: Benjamin
authors.initials: B
authors.lastname: Vinodson
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
authors.forename: Usamah
authors.initials: U
authors.lastname: Kazmi
authors.forename: Tajamul
authors.initials: T
authors.lastname: Hussain
authors.forename: Hossam M
authors.initials: HM
authors.lastname: Draz
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D018912:Arabs / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012529:Saudi Arabia
chemical_list: D052250:Nitric Oxide Synthase Type III