Variants in Follicle-Stimulating Hormone Receptor Gene in Infertile Brazilian Men and the Correlation to FSH Serum Levels and Sperm Count

Ghirelli-Filho, Milton; Peluso, Carla; Christofolini, Denise Maria; Gava, Marcello; Glina, Sidney; Barbosa, Caio Parente; Bianco, Bianca

doi:10.1177/1933719111432872

Cited by 10 publications

(9 citation statements)

References 32 publications

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“…At present, the association between FSHR gene polymorphisms and the risk of male infertility has been reported both in China and abroad, the conclusions from these studies have been inconsistent. Some studies have reported no significant association between the FSHR gene Thr307Ala and Asn680Ser polymorphisms and male infertility, and found that these polymorphisms also had no effect on serum FSH level or semen quality (Ghirelli-Filho et al, 2012). However, Shimoda et al (2009) and Safarinejad et al (2011) reported that the combination genotypes Thr/Ala-Ser/Asn increased the risk of male infertility.…”

Section: Discussionmentioning

confidence: 94%

FSHR gene Thr307Ala and Asn680Ser polymorphisms in infertile men: an association study in North China and meta-analysis

Wu¹,

Xu²,

Wang³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Male infertility is a complex multifactorial and polygenic disease, and genetic factors play an important role in its formation and development. Recently, the association between follicle stimulating hormone receptor (FSHR) gene polymorphisms and male infertility risk has attracted widespread attention due to the unique biological functions of FSH. The aim of this study was to further explore the associations between the Thr307Ala and Asn680Ser polymorphisms of the FSHR gene and male infertility. A case-control study of 212 infertile and 164 fertile men from North China was performed. FSHR polymorphism genotypes were obtained through direct DNA sequencing. A metaanalysis was also performed. In the single-site association analysis, no significant associations were identified between FSHR Thr307Ala and Asn680Ser polymorphisms and male infertility (P > 0.05). However, we found that the combined genotypic frequency of Thr/Ala + Asn/ Asn was higher in infertile patients than in controls (6.6 vs 1.8%; odds ratio (OR) = 3.795; 95% confidence interval (CI): 1.072-13.434, P = 0.027). In the meta-analysis, there was also no evidence of FSHR polymorphism (rs 6165 and rs 6168) association with male infertility 5593 FSHR gene polymorphisms and male infertility in China ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 5592-5601 (2015) (P > 0.05). However, we found that the combined genotypes Thr/Thr + Asn/Asn had an increased risk of male infertility (OR = 1.238; 95%CI: 1.001-1.537, P = 0.049). Our studies further confirmed reports that there were no significant associations between the FSHR Thr307Ala and Asn680Ser polymorphisms and male infertility risk. However, a combined FSHR genotype showed significant association with male infertility.

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Section: Discussionmentioning

confidence: 94%

FSHR gene Thr307Ala and Asn680Ser polymorphisms in infertile men: an association study in North China and meta-analysis

Wu¹,

Xu²,

Wang³

et al. 2015

Genet. Mol. Res.

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“…A total of 15 studies, 4 studies from Asian population [ 24 , 28 – 30 ] and 11 studies from non-Asian population [ 1 , 13 , 14 , 16 , 17 , 22 , 31 – 35 ], met the inclusion criteria (Fig. 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Worldwide, approximately 15% of couples cannot have a child, and in half of the cases the reason is the result of male infertility [ 1 ], which is a complex disorder caused by genetic, developmental, endocrine, or environmental factors or still unknown etiology [ 2 ]. It has been demonstrated that approximately 30% of infertility cases could be attributed to genetic defects, such as Klinefelter syndrome (KS), disorders of sexual development (DSD), or congenital absence of the vas deferens.…”

Section: Introductionmentioning

confidence: 99%

The susceptibility of FSHB -211G > T and FSHR G-29A, 919A > G, 2039A > G polymorphisms to men infertility: an association study and meta-analysis

Zhang

Zhu

et al. 2017

BMC Med Genet

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BackgroundMale infertility is a complex disorder caused by genetic, developmental, endocrine, or environmental factors as well as unknown etiology. Polymorphisms in the follicle stimulating hormone beta subunit (FSHB) (rs10835638, c.-211G > T) and follicle stimulating hormone receptor (FSHR) (rs1394205, c.-29G > A; rs6165, c.919A > G; rs6166, c.2039 A > G) genes might disturb normal spermatogenesis and affect male reproductive ability.MethodsTo further ascertain the aforementioned effects, we conducted a case-control study of 255 infertile men and 340 fertile controls from South China using the Mass ARRAY method, which was analyzed by the t-tests and logistic regression analysis using SPSS for Windows 14.0. In addition, a meta-analysis was performed by combining our results with previous reports using STATA 12.0.ResultsIn the FSHB or FSHR gene single nucleotide polymorphism (SNP) evaluation, no statistically-significant difference was found in the frequency of allelic variants or in genotype distribution between cases and controls. However, a significant association for the comparison of GAA (P: 0.022, OR: 0.63, 95%CI: 0.43–0.94) was seen between the oligozoospermia and controls in haplotype analysis of rs1394205/rs6165/rs6166. In the meta-analysis, rs6165G allele and rs6166 GG genotype were associated with increased risk of the male infertility.ConclusionsThis study suggested that FSHR GAA haplotype would exert protective effects against male sterility, which indicated that the combination of three SNP genotypes of FSHR was predicted to have a much stronger impact than either one alone. Then in the meta-analysis, a significant association was seen between FSHR rs6165, rs6166 polymorphisms and male infertility. In terms of male infertility with multifactorial etiology, further studies with larger sample sizes and different ethnic backgrounds or other risk factors are warranted to clarify the potential role of FSHB and FSHR polymorphisms in the pathogenesis of male infertility.

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“…Different studies reported no significant correlation among serum FSH levels, semen characteristics or fertility status and FSHR gene polymorphisms [7,10,14,22]. However, the hypothesis that the combination of heterozygous FSHR (codon 307 and 607) can be responsible for male infertility was reported by Shimoda et al [11].…”

Section: Discussionmentioning

confidence: 99%

“…There are three common FSHR gene polymorphisms: one in the promoter region (at nucleotide position 29) and two in exon 10 [6]; the first SNP in exon 10 is located in the extracellular domain at position 307 (nucleotide 919) which can be occupied either by alanine (Ala) or by threonine (Thr), the second is located in the intracellular domain at position 680 (nucleotide 2039) and has either asparagine (Asn) or serine (Ser). A decrease in testicular FSHR binding ability has been reported in infertile men, but investigations on the distribution of the above mentioned variants gave conflicting results [7], showing the importance of ethnic differences [8][9][10]. Although no significant correlation between serum FSH levels and semen characteristics and FSHR gene polymorphisms was found, in some studies the combination of heterozygous Thr/Ala + Asn/Ser genotypes has been shown to increase the risk of male infertility [7,11,12].…”

Section: Introductionmentioning

confidence: 99%

Alterations of the FSH and LH receptor genes and evaluation of sperm ultrastructure in men with idiopathic hypergonadotropic hypogonadism

Collodel

Cantara

Cairano

et al. 2013

J Assist Reprod Genet

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Purpose Gonadotropins, interacting with their gonadal receptors, play a key role in sexual development, reproductive functions and metabolism. In this study we performed the genetic analysis of FSHR and LHR and semen investigation in 14 infertile men with normal level of T and elevated levels of FSH and/or LH in the absence of other causes of infertility. Methods Sperm parameters were analysed following WHO (2010) guidelines and sperm morphology by Transmission Electron Microscopy (TEM) analysis mathematically elaborated. FSHR and LHR gene mutations have been searched by PCR technique, followed by DHPLC analysis and direct sequencing.Results In FSHR, we found no difference in the frequency between Ala or Thr at position 307, Ser was at codon 680 in all subjects. Three patients had an heterozygous mutation at codon 419. Three intronic polymorphisms (rs2091787, rs6708637, rs1922464) were significantly found compared to controls; the single allele frequency and the odds ratio were calculated. Two new variants: the Cys338Arg and the Gln123Glu were detected in two different patients. Regarding LHR, three patients were heterozygous for the known variant Glu354Lys and two for Ile374Thr. Intronic polymorphisms were not identified. A new variant, the Val144Ile was found. By the routine semen analysis, variable seminal conditions in this group of patients was observed, on the contrary TEM data mathematically elaborated showed a homogeneous decrease in fertility index and increase in sperm pathologies such as apoptosis and immaturity. Conclusions The obtained results suggest that a deeper examination of spermatozoa, achieved by the use of more powerful tools such as TEM or molecular analysis, are advisable in patients with hypergonadotropic hypogonadism.

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Variants in Follicle-Stimulating Hormone Receptor Gene in Infertile Brazilian Men and the Correlation to FSH Serum Levels and Sperm Count

Cited by 10 publications

References 32 publications

FSHR gene Thr307Ala and Asn680Ser polymorphisms in infertile men: an association study in North China and meta-analysis

FSHR gene Thr307Ala and Asn680Ser polymorphisms in infertile men: an association study in North China and meta-analysis

The susceptibility of FSHB -211G > T and FSHR G-29A, 919A > G, 2039A > G polymorphisms to men infertility: an association study and meta-analysis

Alterations of the FSH and LH receptor genes and evaluation of sperm ultrastructure in men with idiopathic hypergonadotropic hypogonadism

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