Polymorphisms in MTHFR, MS and CBS Genes and Homocysteine Levels in a Pakistani Population 英文参考文献.docVIP
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Polymorphisms in MTHFR, MS and CBS Genes and Homocysteine Levels in a Pakistani Population 英文参考文献
PolymorphismsinMTHFR,MSandCBSGenesand
HomocysteineLevelsinaPakistaniPopulation
MohsinYakub1,NaushadMoti1,SiddiqaParveen1,BushraChaudhry1,IqbalAzam2 ,Mohammad
PerwaizIqbal1*
1DepartmentofBiologicalandBiomedicalSciences,AgaKhanUniversity,Karachi,Pakistan,2DepartmentofCommunityHealthSciences,AgaKhanUniversity,Karachi,
Pakistan
Abstract
Background: Hyperhomocysteinemia (.15mmol/L) is highly prevalent in South Asian populations including Pakistan. In
order to investigate the genetic determinants of this condition, we studied 6 polymorphisms in genes of 3 enzymes -
methylenetetrahydrofolate reductase (MTHFR; C677T; A1298C), methionine synthase (MS; A2756G), cystathionine-b-
synthase (CBS; T833C/844ins68, G919A) involved in homocysteine metabolism and investigated their interactions with
nutritionalandenvironmentalfactorsinaPakistanipopulation.
Methodology/Principal Findings: Inacross-sectional survey, 872healthyadults(355 malesand517females;age 18–60
years)wererecruitedfromalow-incomeurbanpopulationinKarachi.Fastingvenousbloodwasobtainedandassessedfor
plasma/serumhomocysteine;folate,vitaminB12,pyridoxalphosphateandbloodlead.DNAwasisolatedandgenotyping
was performed by PCR-RFLP (restriction-fragment-length- polymorphism) based assays. The average changes in
homocysteine levels for MTHFR 677CT and TT genotypes were positive [b(SE b), 2.01(0.63) and 16.19(1.8) mmol/L,
respectively].ContrarytoMTHFRC677Tpolymorphism,theaveragechangesinplasmahomocysteinelevelsforMS2756AG
andGGvariantswerenegative[b(SEb),20.56(0.58)and20.83(0.99)mmol/L,respectively].Theaveragechangeoccurring
for CBS 844ins68 heterozygous genotype (ancestral/insertion) was 21.88(0.81) mmol/L. The combined effect of MTHFR
C677T,MSA2756GandCBS844ins68genotypesforplasmahomocysteinelevelswasadditive(pvalue,0.001).Oddsof
havinghyperhomocysteinemiawithMTHFR677TTgenotypewas10-foldcomparedtoMTHFR677CCgenotype[OR(95%CI);
10.17(3.6–28.67)]. Protective effect towards hyperhomocysteinemia was observed with heterozygo
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