title: Lower incidence of nonsyndromic cleft lip with or without cleft palate in females: is homocysteine a factor?
abstract: In India, as in other parts of the world, nonsyndromic cleft lip with or without cleft palate (NSCL +/- P) is a highly prevalent birth defect, its incidence in males being twice that in females. A case-control association study has been carried out with respect to homocysteine level and MTHFR C677T, A1298C and SLC19A1 (RFC1) G80A genotypes from an eastern Indian cohort to investigate whether Hcy and other Hcy-pathway genes also contribute to the risk level. While MTHFR 677T and SLC19A1 80G are individually and cumulatively risk factors, SLC19A1 80A appears to be protective against MTHFR 677T risk allele. Elevated Hcy associates with NSCL +/- P both in case mothers and cases. Significantly, this difference shows a gender bias: the level of elevation of Hcy in female cases is distinctly higher than in males, and more case females are hyperhomocyteinemic than the case males. It implies that compared with the males, higher level of Hcy is needed for NSCL +/- P to manifest in the females. We consider this as one of the possible factors why the incidence of this disorder in females is much lower than in males.
authors: Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, India.
authors: Priyanka
authors: P
authors: Kumari
authors: Akhtar
authors: A
authors: Ali
authors: Krishna K
authors: KK
authors: Sukla
authors: Subodh K
authors: SK
authors: Singh
authors: Rajiva
authors: R
authors: Raman
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002971:Cleft Lip / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D002972:Cleft Palate / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D015994:Incidence; D007194:India / Q000453:epidemiology; D007223:Infant; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D058978:Reduced Folate Carrier Protein / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D006710:Homocysteine; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
references: J Inherit Metab Dis. 2011 Feb;34(1):75-81
references: 20814827
references: Eur J Clin Nutr. 2012 Jan;66(1):111-8
references: 21878957
references: Am J Obstet Gynecol. 2003 Oct;189(4):1155-60
references: 14586370
references: Annu Rev Med. 1998;49:31-62
references: 9509248
references: Am J Clin Nutr. 2006 Mar;83(3):701-7
references: 16522920
references: Braz J Med Biol Res. 2008 Aug;41(8):689-93
references: 18797703
references: Mol Genet Metab. 2000 Aug;70(4):310-5
references: 10993718
references: Am J Med Genet A. 2007 May 1;143A(9):952-60
references: 17431894
references: Teratology. 1999 Nov;60(5):253-7
references: 10525201
references: Am J Hum Genet. 2002 Mar;70(3):758-62
references: 11781870
references: Pediatr Res. 2009 Nov;66(5):501-6
references: 19668105
references: In Vitro Cell Dev Biol Anim. 2003 Jan-Feb;39(1-2):98-105
references: 12892533
references: J Hum Genet. 2006;51(4):278-283
references: 16489479
references: Am J Obstet Gynecol. 1999 Mar;180(3 Pt 1):660-4
references: 10076144
references: Birth Defects Res A Clin Mol Teratol. 2011 Jan;91(1):50-60
references: 21254359
references: BMJ. 2007 Mar 3;334(7591):464
references: 17259187
references: Birth Defects Res A Clin Mol Teratol. 2011 Mar;91(3):153-61
references: 21290562
references: J Nutr. 2003 Aug;133(8):2643-9
references: 12888652
references: Annu Rev Med. 2009;60:39-54
references: 18729731
references: J Hum Genet. 2005;50(12):655-63
references: 16244782
references: Genet Test Mol Biomarkers. 2009 Jun;13(3):355-60
references: 19419265
references: Lancet. 2009 Nov 21;374(9703):1773-85
references: 19747722