Analysis of the candidate genes responsible for non-syndromic cleft lip and palate in Japanese people

Abstract

In order to assess the association of alleles for candidate genes with non-syndromic cleft lip and palate, DNA samples from 43 Japanese patients were compared with those from 73 control subjects with respect to the genes encoding transforming growth factor alpha (TGFalpha), TGFbeta and gamma-aminobutyric acid type A receptor beta3 (GABRB3). The restriction fragment length polymorphisms of the 3'-non-coding region of the TGFalpha gene K-primer region were observed after digestion with NcoI and HinfI. Allele 4 was the most common among cases of cleft lip with or without cleft palate, whereas allele 2 was the most common among controls. A significant difference was found in this region between groups with cleft lip (with or without cleft palate) and controls (chi2=10.190; P=0.017). Three alleles of the TGFbeta2 gene were tested, and allele 2 was the most common in both cases and controls. The proportion of allele 2 in the case group was greater than that in the control group, showing a significant difference between cases of cleft lip (with or without cleft palate) and controls (chi(2)=19.208; P<0.0001). No significant differences in variants of TGFbeta3 or GABRB3 between case and control populations were observed. Thus it is concluded that TGF genes play a role in craniofacial development, and that alleles of TGFalpha or/and TGFbeta2 are associated with cleft lip and cleft palate in Japanese populations.

TGFB3 displays parent-of-origin effects among central Europeans with nonsyndromic cleft lip and palate

“…Consistent with this hypothesis, Tgf-b3 -/-knockout mice present with a developmental defect of the secondary palate (Proetzel et al 1995). In humans, however, evidence for any involvement of the TGFB3 gene in development of oral clefts has remained inconclusive, with reports of significant (Maestri et al 1997;Lidral et al 1998;Romitti et al 1999;Mitchell et al 2001;Sato et al 2001;Beaty et al 2002;Scapoli et al 2002;Jugessur et al 2003;Kim et al 2003;Slayton et al 2003;Vieira et al 2003;Suzuki et al 2004) as well as negative (Lidral et al 1997;Tanabe et al 2000;Beaty et al 2001;Morkūniené et al 2007) associations among different populations with nonsyndromic orofacial clefts. In this study, we investigated whether the results of Ichikawa et al (2006), who conducted the most comprehensive study of TGFB3 to date, were also apparent in CL/P families of central European descent.…”

“…Mice with a genetic deletion of Tgf-b3 (-/-) present with either complete cleft palate or severe partial cleft palate (Kaartinen et al 1995;Proetzel et al 1995). Genetic association studies in humans of different ethnicities suggest TGFB3 may be involved in the formation of orofacial clefts (Maestri et al 1997;Lidral et al 1998;Romitti et al 1999;Mitchell et al 2001;Sato et al 2001;Beaty et al 2002;Scapoli et al 2002;Jugessur et al 2003;Kim et al 2003;Slayton et al 2003;Vieira et al 2003;Suzuki et al 2004), although negative studies have also been reported (Lidral et al 1997;Tanabe et al 2000;Beaty et al 2001;Morkūniené et al 2007). Until recently, most studies used a CA repeat located 61.215 bp upstream from translation starting point of TGFB3 as well as a VNTR marker in the 5 0 untranslated region (UTR) (D at -21083 to -21086 (AGAGGG repeat)) and with X5.1 a T [ C substitution [ref.…”

TGFA/Taq I polymorphism and environmental factors in non-syndromic oral clefts in Southern Brazil

“…A mutant allele shows a four-base (TAAT) deletion changing the 178 bp C1 allele to the 174 bp C2 allele. 9 The first evidence for an association between specific TGFA alleles and non-syndromic CL ± P came from a Caucasian population in the state of Iowa. 10 The association has been confirmed in several populations from different regions of the world.…”

Conscious Sedation in Minor Oral Surgery with Midazolam IV Versus Nasal Spray a Comparative Study

“…Figure 4 with placebo in a randomized study in 50 patients undergoing oral surgical procedures under local anaesthesia and stated that systolic and diastolic blood pressures fall by approximately 11 and 5 mm of Hg, respectively, in the midazolam group. In their study Rodrigo et al [12] compared patient-controlled sedation with 1-mg increments of midazolam at 1-min intervals with 0.1-mg increments of midazolam without a lock-out interval in thirtytwo patients with age of 17-35 years having third molar surgery and stated that there was slight decrease in blood pressure in both groups.…”

“…Forster et al [10] used intra venous midazolam as an induction agent for anaesthesia and stated that, midazolam, 0.15 mg/kg IV over 15 secs, produces statistically significant increase in pulse rate (18%). Similarly, Rodrigo et al [12] compared patient-controlled sedation with 1-mg increments of midazolam at 1-min intervals with 0.1-mg increments of midazolam without a lock-out interval in thirty-two patients with age of 17-35 years, having third molar surgery and stated that there was increase in pulse rate in both groups after injection of local anaesthesia. On contrary in their study Dixon et al [9] used sedation for local anaesthesia and compared intravenous midazolam and diazepam and stated that there was no significant change in pulse rate following production of satisfactory sedation.…”