The role of MSH5 C85T and MLH3 C2531T polymorphisms in the risk of male infertility with azoospermia or severe oligozoospermia.
BACKGROUND
The mismatch repair proteins MSH5 and MLH3 play a crucial role in spermatogenesis. We tested this hypothesis by examining the contribution of functional polymorphisms in MSH5 C85T and MLH3 C2531T to the risk of male infertility.


METHODS
We investigated Chinese patients, including 162 infertile individuals with idiopathic azoospermia or severe oligozoospermia, and 160 fertile men as controls.


RESULTS
We observed an increased risk of male infertility associated with the MSH5 (CT+TT) (OR, 2.51; 95% CI, 1.43-4.40; P<0.001) or MLH3 (CT+TT) (OR, 1.98; 95% CI, 1.23-3.17; P<0.001) genotype, compared to the MSH5 CC or MLH3 CC genotype, respectively. Interactions between these MSH5 and MLH3 polymorphisms increased the risk of male infertility in a multiplicative manner, with the OR being 6.78 (95% CI, 2.12-21.68) for subjects carrying both MSH5 (CT+TT) and MLH3 (CT+TT) genotypes.


CONCLUSIONS
There is an association of polymorphism C85T in MSH5 or C2531T in MLH3 with male infertility, specifically azoospermia or severe oligozoospermia, and interaction between these MSH5 and MLH3 polymorphisms increased the risk of developing male infertility. Therefore, the MSH5 and MLH3 polymorphisms may be genetic determinants for human spermatogenesis impairment.
Xu
Keqian
K
Department of Clinical Biochemistry, Xiangya School of Medicine, Central South University, 172 Tongzipo Rd, Changsha, Hunan, 410013, China. xukeqian@126.com
Lu
Tingting
T
Zhou
Hui
H
Bai
Lihong
L
Xiang
Yaoyun
Y
D053713:Azoospermia / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D002681:China; D017931:DNA Primers; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D000070956:MutL Proteins; D020641:Polymorphism, Single Nucleotide
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D017931:DNA Primers; C403623:MLH3 protein, human; C118481:MSH5 protein, human; D000070956:MutL Proteins