The I105V polymorphism in glutathione S-transferase P1, parental smoking and the risk for nonsyndromic cleft lip with or without cleft palate

Abstract

Genetic variations in the detoxification enzyme glutathione S-transferase P1 (GSTP1) may modify the teratogenicity of lifestyles, such as smoking. We investigated the role of the I105V polymorphism in GSTP1, parental periconception smoking, and their interaction with nonsyndromic cleft lip with or without cleft palate (CL/P) risk in the offspring. The GSTP1 I105V polymorphisms were determined in Dutch nonconsanguineous Caucasians comprising of 155 CL/P triads (mother, father, child) and 195 control triads. The analyses were also carried out on complete triads only (n ¼ 69 CL/P and n ¼ 95 controls). Transmission disequilibrium testing and logistic regression analyses were performed. Neither maternal nor paternal smoking increased CL/P risk; odds ratios (OR): 1.2, 95 confidence intervals (CI) ¼ 0.7-2.0 and OR: 1.0, 95% CI ¼ 0.6-1.6, respectively. Carriership of the polymorphic Val105 allele in mothers may increase CL/P risk, OR: 1.5, 95% CI ¼ 0.96-2.5. Children homozygous for the Val105 allele may show an increased risk of CL/P, OR: 2.2, 95% CI ¼ 0.8-6.4. Maternal smoking tended to increase CL/P risk in mothers and children carrying Val105 alleles, OR ¼ 1.9, 95% CI ¼ 0.9-4.0 and OR ¼ 2.2, 95% CI ¼ 0.98-4.9, respectively. The highest risk for CL/P in children carrying Val105 alleles with a smoking father was 1.7, 95% CI ¼ 0.8-3.5. The GSTP1 I105V polymorphism in mothers and/or children either alone or in combination with maternal smoking may contribute to CL/P risk. Although of borderline significance, these results may underline the importance of smoking cessation in the periconception period for the prevention of CL/P in future generations.

Genome-wide analysis of parent-of-origin effects in non-syndromic orofacial clefts

“…In this regard, it is interesting to note effects of maternal genotype and maternalspecific environmental modifiers such as smoking, drinking and vitamin intake during pregnancy on oral cleft susceptibility have been previously reported in various studies. 2,[10][11][12][13][14][15][16][17][18][19] However, it should be noted that the parental asymmetry tests we applied here do not specifically test for maternal effects which would be expected to occur via alterations of the in utero environment. Calculation of genomic inflation factors for the MAT and PAT tests showed a small increase for the MAT compared with the PAT in all categories, this increased inflation factor in the MAT does not discern the underlying cause, being consistent with either a true excess of biological associations with the maternally inherited alleles, or alternatively differing population structure between the two parental populations.…”

“…In fact, environmental studies have indicated maternal smoking, and potentially alcohol consumption, during pregnancy greatly increase the risk of clefting in offspring, with some evidence of genetic interactions. 2,10,11 Similarly, according to several studies, multi-vitamin supplements with or without folic acid taken during pregnancy have been shown to decrease the risk of oral clefting, with a stronger effect seen in CL/P as compared with CPO. [12][13][14] If levels of circulating folate are influenced by genetic factors, then it can be hypothesized any maternal genes involved in dictating circulating folate levels could also alter the risk of OFCs in the fetus.…”

Nicotine Exposure During Pregnancy Results in Persistent Midline Epithelial Seam With Improper Palatal Fusion

“…25 Meanwhile, polymorphisms of several genes, including MSX1, TGFB3, BCL3, CYP1A1, GSTP1, and GSTT1 have been examined in conjunction with maternal alcohol consumption, cigarette smoking, medication use, and multivitamin supplementation during pregnancy. [25][26][27] It was shown that smoking by both parents interacts with a specific allelic variant of MSX1, which significantly increase the OFC risk for their offspring. 28 Moreover, a novel approach was developed by Wehby et al 26 to study the role of maternal smoking and OFC, in which they found out that smoking before and during pregnancy increased the risk of OFC by about 4-5 times at the sample average smoking rate.…”

Interferon Regulatory Factor 6 (IRF6) and Gene – Environment Interactions in Non-Syndromic Orofacial Cleft Cases in Saudi Arabia-A Case Control Study

“…The factors that were studied were mainly folic acid and vitamin supplements, smoking, and maternal passive smoking. Furthermore, only a small number of gene variants were analyzed [25][26][27][28]. In our study, we focused on the interaction between environmental factors and maternal genes to assess any direct maternal effect occurring during pregnancy.…”