Montenegro Marcelo F, Barbosa Fernando, Sandrim Valeria C, Gerlach Raquel F, Tanus-Santos Jose E
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil-FMRP-USP, Av. Bandeirantes, 3900, Monte Alegre, CEP 14049-900, Ribeirao Preto, SP, Brazil.
Clin Chim Acta. 2006 May;367(1-2):192-5. doi: 10.1016/j.cca.2005.12.009. Epub 2006 Jan 30.
delta-Aminolevulinic acid dehydratase (ALAD) catalyzes the second step of heme synthesis. The ALAD gene shows a polymorphism (G-to-C transversion at position 177) leading to 2 alleles (ALAD1 and ALAD2) and 3 phenotypes (ALAD 1-1, ALAD 1-2 and ALAD 2-2). This polymorphism has been shown to affect lead toxicity and the risk of meningioma. In addition, there is little evidence showing interethnic differences in the distribution this polymorphism, especially in heterogeneous populations such as the present-day Brazilian population. We examined the distribution of genetic variants of the G177C ALAD polymorphism in black and white Brazilians.
We studied 115 subjects self-reported as black and 119 subjects as white (total N=234; 135 men and 99 women; age range: 18-60 years). Genomic DNA was extracted from venous blood and the genotypes for the ALAD polymorphism were determined by PCR followed by RFLP digestion and gel electrophoresis.
We found a notable interethnic disparity in the distribution of G177C ALAD genotypes and alleles. The ALAD2 allele was more common in whites (12%) than in blacks (4%) (P<0.05). Correspondingly, the heterozygote (ALAD 1-2) or homozygote variant (ALAD 2-2) genotypes for this polymorphism were more common in whites than in blacks (P<0.05).
The significant interethnic differences in the distribution of G177C ALAD variants found in the Brazilian population is consistent with differences previously reported in other countries. These findings may help us understand the interethnic disparities in susceptibility to lead toxicity and brain tumors.
δ-氨基乙酰丙酸脱水酶（ALAD）催化血红素合成的第二步。ALAD基因存在一种多态性（第177位发生G到C的颠换），导致产生2个等位基因（ALAD1和ALAD2）和3种表型（ALAD 1-1、ALAD 1-2和ALAD 2-2）。这种多态性已被证明会影响铅毒性和患脑膜瘤的风险。此外，几乎没有证据表明这种多态性的分布存在种族间差异，尤其是在像当代巴西人群这样的异质人群中。我们研究了巴西黑人和白人中G177C ALAD多态性的基因变异分布情况。
我们研究了115名自称是黑人的受试者和119名自称是白人的受试者（总计N = 234；135名男性和99名女性；年龄范围：18至60岁）。从静脉血中提取基因组DNA，通过聚合酶链反应（PCR），随后进行限制性片段长度多态性（RFLP）消化和凝胶电泳来确定ALAD多态性的基因型。
我们发现G177C ALAD基因型和等位基因的分布存在显著的种族间差异。ALAD2等位基因在白人中（12%）比在黑人中（4%）更常见（P < 0.05）。相应地，这种多态性的杂合子（ALAD 1-2）或纯合子变异（ALAD 2-2）基因型在白人中比在黑人中更常见（P < 0.05）。
在巴西人群中发现的G177C ALAD变异分布的显著种族间差异与其他国家先前报道的差异一致。这些发现可能有助于我们理解种族间在铅毒性易感性和脑肿瘤方面的差异。
