Analysis of heat shock protein 70 gene polymorphisms Mexican patients with idiopathic pulmonary fibrosis.
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown etiology. Genetic variation within different major histocompatibility complex (MHC) loci contributes to the susceptibility to IPF. The effect of 70 kDa heat shock proteins (HSP70) gene polymorphisms in the susceptibility to IPF is unknown. The aim of this study was to explore the association between HSP70 polymorphisms and IPF susceptibility in the Mexican population.


METHODS
Four HSP70 single nucleotide polymorphisms (SNPs) were evaluated using real time PCR assays in 168 IPF patients and 205 controls: +2763 C>T of HSPA1L (rs2075800), +2437 of HSP HSPA1L A>G (rs2227956), +190 of HSPA1A G>C (rs1043618) and +1267 of HSPA1B G>A (rs1061581).


RESULTS
The analysis of the recessive model revealed a significant decrease in the frequency of the genotype HSPA1B AA (rs1061581) in IPF patients (OR = 0.27, 95 % CI = 0.13-0.57, Pc = 0.0003) when compared to controls. Using a multivariate logistic regression analysis in a codominant model the HSPA1B (rs1061581) GA and AA genotypes were associated with a lower risk of IPF compared with GG (OR = 0.22, 95 % CI = 0.07-0.65; p = 0.006 and OR = 0.17, 95 % CI = 0.07-0.41; p = <0.001). Similarly, HSPA1L (rs2227956) AG genotype (OR = 0.34, 95 % CI = 0.12-0.99; p = 0.04) and the dominant model AG + GG genotypes were also associated with a lower risk of IPF (OR = 0.24, 95 % CI = 0.08-0.67; p = 0.007). In contrast, the HSPA1L (rs2075800) TT genotype was associated with susceptibility to IPF (OR = 2.52, 95 % CI = 1.32-4.81; p = 0.005).


CONCLUSIONS
Our findings indicate that HSPA1B (rs1061581), HSPA1L (rs2227956) and HSPA1 (rs1043618) polymorphisms are associated with a decreased risk of IPF.
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas" Tlalpan 4502, Col. Sección XVI, 14080, Mexico, México. araquiga@yahoo.com.mx.
Arnoldo
A
Aquino-Gálvez
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas" Tlalpan 4502, Col. Sección XVI, 14080, Mexico, México. ggonzalezavila@yahoo.com.
Georgina
G
González-Ávila
Hospital General de México, Universidad Nacional Autónoma de México, Laboratorio de Inmunología, Mexico, Mexico. meperezrodriguez@yahoo.com.mx.
Martha
M
Pérez-Rodríguez
Unidad de Investigación Médica en Inmunología, CMN S-XXI Instituto Mexicano del Seguro Social, Mexico, Mexico. oswpartida@yahoo.com.mx.
Oswaldo
O
Partida-Rodríguez
Unidad de Investigación Médica en Inmunología, CMN S-XXI Instituto Mexicano del Seguro Social, Mexico, Mexico. mirnieves@yahoo.com.mx.
Miriam
M
Nieves-Ramírez
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas" Tlalpan 4502, Col. Sección XVI, 14080, Mexico, México. pirami07@yahoo.com.
Inocencio
I
Piña-Ramírez
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas" Tlalpan 4502, Col. Sección XVI, 14080, Mexico, México. grmunam@yahoo.com.mx.
Gustavo
G
Ramírez-Martínez
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas" Tlalpan 4502, Col. Sección XVI, 14080, Mexico, México. mcastillejos@gmail.com.
Manuel
M
Castillejos-López
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas" Tlalpan 4502, Col. Sección XVI, 14080, Mexico, México. marc_checa@yahoo.com.
Marco
M
Checa
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas" Tlalpan 4502, Col. Sección XVI, 14080, Mexico, México. vicoruz@yahoo.com.mx.
Victor
V
Ruiz
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas" Tlalpan 4502, Col. Sección XVI, 14080, Mexico, México. franciscojavierurrea@hotmail.com.
Francisco
F
Urrea
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas" Tlalpan 4502, Col. Sección XVI, 14080, Mexico, México. bsommerc@hotmail.com.
Bettina
B
Sommer
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas" Tlalpan 4502, Col. Sección XVI, 14080, Mexico, México. joazu@yahoo.com.
Joaquin
J
Zúñiga
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas" Tlalpan 4502, Col. Sección XVI, 14080, Mexico, México. mselmanl@yahoo.com.mx.
Moisés
M
Selman
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008800:Mexico; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide
D018840:HSP70 Heat-Shock Proteins; C490786:HSPA1A protein, human; C525621:HSPA1B protein, human; C543454:HSPA1L protein, human