The N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes involved in the metabolism of drugs, environmental toxins and the aromatic amine carcinogens present in cigarette smoke. Genetic variations in NAT2 have long been recognized as the cause of variable enzymatic activity or stability, leading to slow or rapid acetylation. In the present study, we genotyped three single-nucleotide polymorphisms (SNPs) from the NAT2 gene (rs1799929, rs1799930 and rs1799931), using TaqMan allelic discrimination, among 212 individuals from six major South Indian populations and compared the results with other available Indian and worldwide data. All three of the markers followed Hardy–Weinberg equilibrium and were highly polymorphic in the studied populations. The constructed haplotypes showed a high level of heterozygosity. All of the populations in the present study commonly shared only four haplotypes out of the eight possible three-site haplotypes. The haplotypes exhibited fairly high frequencies across multiple populations, where three haplotypes were shared by all six populations with a cumulative frequency ranging from 88.2% (Madiga) to 97.0% (Balija). We also observed a tribal-specific haplotype. A strong linkage disequilibrium (LD) between rs1799929 and rs1799930 was consistent in all of the studied populations, with the exception of the Madiga. A comparison of the genomic regions 20-kb up- and downstream of rs1799930 in a large number of worldwide samples showed a strong LD of this SNP with another NAT2 SNP, rs1112005, among the majority of the populations. Moreover, our lifestyle test (hunter–gatherer versus agriculturist) in comparison with the NAT2 variant suggested that two of the studied populations (Balija and Madiga) have likely shifted their diet more recently.
Background: Glutathione S-transferases (GSTs) are members of the phase II biotransformation enzymes that play a key role in cellular detoxification of chemical carcinogens and xenobiotics. Variations at GST genes have been reported in different human populations, and some association studies have reported increased risk for cancers and other disease end points. The present study was conducted to investigate the allele frequency variations in south Indian populations.
The current study observed significant differences in the frequency of the CBS 844ins68 allele across populations. There is a significant association between CBS c.844ins68 polymorphism and cleft lip and palate in the Indian population. Additional studies are warranted to identify the functional variants in the genes controlling homocysteine as etiological contributors to the formation of oral clefts.
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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