Consistent interethnic differences in the distribution of clinically relevant endothelial nitric oxide synthase genetic polymorphisms

Marroni, Aline S.; Metzger, Ingrid F.; Souza-Costa, Debora C.; Nagassaki, Sabrina; Sandrim, Valéria C.; Corrêa, Ronan Xavier; Rios-Santos, Fabrício; Tanus‐Santos, Jose E.

doi:10.1016/j.niox.2005.02.002

Cited by 136 publications

(103 citation statements)

References 35 publications

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“…2,3 Importantly, we found that the same specific eNOS haplotypes are associated with susceptibility to hypertension in subjects with different ethnic backgrounds, 3 even though significant interethnic differences exist in the distribution of eNOS genotypes or haplotypes. 4,5 Our results support the suggestion that significant interactions between individual eNOS polymorphisms play a role in the genetic susceptibility to hypertension, but not individual eNOS polymorphisms. This conclusion would hardly be drawn with a meta-analysis based on single polymorphism studies, as the one conducted by Zintzaras et al We believe that a meta-analysis based on eNOS haplotypes can lead to more reliable conclusions than that based on eNOS genotypes.…”

Section: Endothelial Nitric Oxide Synthase Polymorphisms and Susceptisupporting

confidence: 84%

Endothelial Nitric Oxide Synthase Polymorphisms and Susceptibility to Hypertension: Genotype Versus Haplotype Analysis

Tanus‐Santos

Casella-Filho

2007

Hypertension

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Zintzaras et al reported interesting results of a meta-analysis of all the available studies on the possible association between endothelial NO synthase (eNOS) polymorphisms and hypertension. 1 They concluded that there is evidence for significant association between the 4b/4a variable number of tandem repeats polymorphism in intron 4 of the eNOS gene and susceptibility to hypertension, without significant influence for other eNOS polymorphisms. 1 Although meta-analysis may shed some light on contradictory results derived from a number of different case-control studies, we believe that haplotype (or diplotype) analysis can provide more relevant biological information. In fact, the analysis of haplotypes (specific combinations of genetic markers within a chromosome cluster location) has been valued as a more powerful approach in association studies than the analysis of single polymorphisms. For example, we have recently reported that eNOS haplotypes involving 3 of the most studied eNOS polymorphisms are associated with the development of hypertension. 2,3 Interestingly, single eNOS polymorphisms were not associated with hypertension in these studies. Therefore, our haplotype findings would have been missed if specific eNOS genotypes alone had been considered. 2,3 Importantly, we found that the same specific eNOS haplotypes are associated with susceptibility to hypertension in subjects with different ethnic backgrounds, 3 even though significant interethnic differences exist in the distribution of eNOS genotypes or haplotypes. 4,5 Our results support the suggestion that significant interactions between individual eNOS polymorphisms play a role in the genetic susceptibility to hypertension, but not individual eNOS polymorphisms. This conclusion would hardly be drawn with a meta-analysis based on single polymorphism studies, as the one conducted by Zintzaras et al. We believe that a meta-analysis based on eNOS haplotypes can lead to more reliable conclusions than that based on eNOS genotypes.

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Section: Endothelial Nitric Oxide Synthase Polymorphisms and Susceptisupporting

confidence: 84%

Endothelial Nitric Oxide Synthase Polymorphisms and Susceptibility to Hypertension: Genotype Versus Haplotype Analysis

Tanus‐Santos

Casella-Filho

2007

Hypertension

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“…It could be due to selection of patient populations from different ethnic groups 23,24 or different interactions of the genetic background with the environmental factors (i.e., cardiovascular risk factors present in the specific patient populations). 25 One of the considerable limitations of these population studies is the lack of information on whether this polymorphism is functional, that is, whether the Glu298Asp variant is associated with reduced NO synthesis.…”

Section: Enos Gene Expression In Atherosclerosis Enos Gene Polymorphimentioning

confidence: 99%

Recent Advances in Understanding Endothelial Dysfunction in Atherosclerosis

Yang

Ming²

2006

Clinical Medicine & Research

172

116

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Over the last two decades, it has become evident that decreased bioavailability of endothelial nitric oxide (NO) produced from endothelial NO synthase (eNOS), referred to as endothelial dysfunction, plays a crucial role in the development and progression of atherosclerosis. Much progress has been made in understanding the mechanisms of decreased endothelial NO bioavailability at the levels of regulation of eNOS gene expression, eNOS enzymatic activity and NO inactivation. Initial studies suggest that increasing eNOS gene expression would improve endothelial NO release in the hope of inhibiting the progression of atherosclerosis. Recent experimental studies, however, do not always support this therapeutic concept and show some evidence that overexpression of eNOS in atherosclerosis may be even harmful for the disease progression.Thus, recent research to improve endothelial function in atherosclerosis has focused on regulation of eNOS enzymatic activity and prevention of NO inactivation by oxidative stress. Since the role of oxidative stress in endothelial NO bioavailability has been reviewed in a large number of comprehensive articles, this article focuses on the relevant regulatory mechanisms of eNOS enzymatic activity that are emerging to play a role in endothelial dysfunction in atherosclerosis.

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“…The NOS3 27-bp VNTR 4 repeat allele occurs more frequently among Africans than the Europeans and other populations [14]. The current study suggests that NOS3 27-bp VNTR is associated with nonsyndromic cleft lip with or without cleft palate in the Indian population.…”

Section: Discussionmentioning

confidence: 49%

Endothelial nitric oxide synthase VNTR (intron 4 a/b) polymorphism association with nonsyndromic oral clefts

Lakkakula¹,

Gurramkonda²,

Lakkakula³

et al. 2013

Turk J Bioch

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Objective: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with substantial clinical and social impact, and whose causes include both genetic and environmental factors. Folate and homocysteine metabolism have been indicated to play a role in the etiology of NSCLP. The aim of this study was to determine the prevalence of NOS3 27-bp VNTR and to evaluate whether this polymorphism contributed to the risk of NSCLP. Material and methods:We studied the 27 base pair tandem repeat polymorphism in intron 4 of the endothelial nitric oxide synthase (NOS3) gene in 230 unrelated individuals belong to 7 Indian populations along with 141 NSCLP cases and 142 unrelated controls. The genotyping was performed by polymerase chain reaction and electrophoresis. The data were statistically analysed using the χ 2 -test. Results: The NOS3 27-bp VNTR 4a allele is present in six of the seven populations analysed and allele frequencies range from 6.8% in Sugali to 23.5% in Madiga populations. NOS3 showed protective association with predisposition towards NSCLP for the heterozygous (4b/a) genotypes (4b/b vs. 4b/a: OR =0.58, 95% CI =0.34 to 0.99, p=0.044). Conclusions:The current study suggests significant differences in the frequency of the NOS3 VNTR allele across the populations. There is protective association between NOS3 27-bp VNTR polymorphism and NSCLP in the Indian population. Key Words: nitric oxide, NOS3, VNTR polymorphism, orofacial clefts, Indians Conflict of Interest: The authors declare that they have no competing interests.. ÖZETAmaç: Semptomatik olmayan damak yarıklı veya yarıksız yarık dudak (NSCLP) olguları sosyal ve klinik etkisi ağır olan ve çok sık rastlanan bir doğum bozukluğu olup, genetik ve çevresel etkenlere bağlıdır. NSCLP etiyolojisinde folat ve homosistin metabolizmalarının etkin olduğu endike edilmiştir. Bu çalışmanın amacı NOS3 27 bp VNTR sıklığının belirlenmesi ve bu polimorfizmin NSCLP için bir risk faktörü olma olasılığının araştırılmasıdır. Materyal ve metod: Hindistanda bulunan 7 toplumdan 141 NSCLP ve 142 ilişkisiz kontrol olmak üzere 230 ilişkilendirlmemiş bireyde nitrik oksit sentaz geninin intron 4 bölgesinde bulunan 27 bazlık ardışık tekrar polimorfizmi incelenmiştir. Genotiplendirme polimeraz zincir reaksiyonu ve elektroforez ile gerçekleştirilmiştir. Istatistiksel veri analizi χ 2 -testi ile yapılmıştır. Bulgular: NOS3 27-bp VNTR 4a alleli incelenen 7 toplumdan altısında bulunmakta ve allel sıklıkları Sugali toplumunda %6.8'den Madiga toplumunda %23.5'e kadar değişmektedir. NOS3 koruyucu assosiyasyon, heterezigot 4b/a genotipleri (4b/b vs. 4b/a: OR = 0.58, 95% CI = 0.34 to 0.99, p=0.044) için NSCLP'e yatkınlık gözlemlenmiştir. Sonuç: Bu çalışmada toplumlar arasında NOS3 VNTR allel sklığında belirgin farklılıklar göstermektedir. Hint toplumu için NOS3 27-bp VNTR polimorfismi ve NSCLP arasında koruyucu asosiyasyon bulunmaktadır. Anahtar Kelimeler: nitrik oksit, NOS3, VNTR polimorfizmi, orofasiyal cepler, Hintliler Çıkar Çatışması: Yazarların çıkar çatışması ...

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Consistent interethnic differences in the distribution of clinically relevant endothelial nitric oxide synthase genetic polymorphisms

Cited by 136 publications

References 35 publications

Endothelial Nitric Oxide Synthase Polymorphisms and Susceptibility to Hypertension: Genotype Versus Haplotype Analysis

Endothelial Nitric Oxide Synthase Polymorphisms and Susceptibility to Hypertension: Genotype Versus Haplotype Analysis

Recent Advances in Understanding Endothelial Dysfunction in Atherosclerosis

Endothelial nitric oxide synthase VNTR (intron 4 a/b) polymorphism association with nonsyndromic oral clefts

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