Costa Marina C, Esteves Francisco, Antunes Francisco, Matos Olga
Unidade de Protozoários Oportunistas/VIH e outras Protozooses, Instituto de Higiene e Medicina Tropical, Rua da Junqueira 96, 1349-008 Lisboa, Portugal.
J Antimicrob Chemother. 2006 Dec;58(6):1246-9. doi: 10.1093/jac/dkl411. Epub 2006 Oct 12.
The aim of the present study was to evaluate the genetic variation of Pneumocystis jirovecii dihydrofolate reductase (DHFR) gene in an immunocompromised Portuguese population and to investigate the possible association between DHFR genotypes and P. jirovecii pneumonia (PcP) prophylaxis with co-trimoxazole.
One hundred and thirty-eight P. jirovecii isolates were submitted to DHFR genetic characterization by PCR and sequencing.
In the studied population, 72.7% of the patients presented sequences identical to the wild-type sequence of the P. jirovecii DHFR gene and 27.3% presented point substitutions. A total of nine substitution sites were identified; four synonymous substitutions at nucleotide positions 201, 272, 312 and 381 were detected in 31 patients. Five non-synonymous substitutions were observed, leading to the DHFR mutations Leu-13-->Ser, Asn-23-->Ser, Ser-31-->Phe, Met-52-->Leu and Ala-67-->Val. With the exception of the polymorphism at position 312 and the mutation at codon 52, all polymorphisms were reported in this study for the first time.
Our results suggest that DHFR gene polymorphisms are frequent in the Portuguese immunocompromised population but do not seem to be associated with PcP prophylaxis failure (P = 0.748 and P = 0.730).
本研究旨在评估葡萄牙免疫功能低下人群中耶氏肺孢子菌二氢叶酸还原酶（DHFR）基因的遗传变异，并探讨DHFR基因型与耶氏肺孢子菌肺炎（PcP）复方新诺明预防之间的可能关联。
138株耶氏肺孢子菌分离株通过聚合酶链反应（PCR）和测序进行DHFR基因特征分析。
在研究人群中，72.7%的患者呈现与耶氏肺孢子菌DHFR基因野生型序列相同的序列，27.3%的患者存在点突变。共鉴定出9个突变位点；在31例患者中检测到核苷酸位置201、272、312和381处的4个同义突变。观察到5个非同义突变，导致DHFR突变Leu-13→Ser、Asn-23→Ser、Ser-31→Phe、Met-52→Leu和Ala-67→Val。除312位的多态性和52密码子处的突变外，本研究首次报道了所有多态性。
我们的结果表明，DHFR基因多态性在葡萄牙免疫功能低下人群中很常见，但似乎与PcP预防失败无关（P = 0.748和P = 0.730）。
