[SMAD4 gene polymorphisms and genetic susceptibility of coal work's pneumoconiosis].
OBJECTIVE
to explore whether 6 tagging single nucleotide polymorphisms (SNPs) within SMAD4 gene were involved in the genetic susceptibility of coal worker's pneumoconiosis (CWP) by case-control study.


METHODS
this study consisted of 438 CWP patients and 448 controls. All study subjects were Han Chinese, underground coal miners and recruited from coal mines of Xuzhou Mining Business Group Co Ltd. The 5 ml venous blood sample was obtained from all studied subjects and extracted genome DNA from the isolated leucocytes. Six SNPs were selected from the HapMap and detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).


RESULTS
the single SNP analyses showed that the genotype frequencies of SMAD4 (rs10502913) was significantly different from those in controls (P < 0.05). Multivariate logistic regression analyses revealed that SMAD4 (rs10502913) AA genotype was associated with increased risk of CWP (adjusted OR = 1.63, 95%CI = 1.00 - 2.69, P = 0.05) and this was evident among subgroups of those smoker (adjusted OR = 2.28, 95%CI = 1.09 ∼ 4.80, P < 0.05) and cases with stage I (adjusted OR = 2.42, 95%CI = 1.41 ∼ 4.14, P < 0.01). The SMAD4 (rs9304407) GG genotype was associated with an decreased risk of CWP (adjusted OR = 0.65, 95%CI = 0.43 ∼ 0.98, P < 0.05) and the further stratification analysis showed that the risk of CWP was decreased in nonsmoking groups.


CONCLUSIONS
our results suggest that individuals with the SMAD4 (rs10502913) AA genotype was associated with an increased risk of CWP. However, carriers of SMAD4 (rs9304407) GG genotype have a protective effect on the developing CWP.
School of Public Health, Nanjing Medical University, Nanjing 210029, China.
Jin
J
Xu
Meng
M
Zhu
Hong-Quan
HQ
Cai
Kai
K
Zhang
Wei-Wei
WW
Duan
Ting
T
Wang
Li
L
Wang
Sha-Sha
SS
Wang
Yang
Y
Ye
Chun-Hui
CH
Ni
D000368:Aged; D055008:Anthracosis / Q000235:genetics*; D016022:Case-Control Studies; D003032:Coal Mining; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051901:Smad4 Protein / Q000235:genetics*
C497796:SMAD4 protein, human; D051901:Smad4 Protein