Genetic and environmental factors in the aetiology of hypospadias

George, Mathew; Schneuer, Francisco J.; Jamieson, Sarra E.; Holland, A.J.A.

doi:10.1007/s00383-015-3686-z

Cited by 22 publications

(18 citation statements)

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“…Congenital hypospadias has been the most challenging field of pediatrics with increasing prevalence worldwide, yielding complicated classifications and high incidence of postoperative complications [ 15 – 17 ]. We measured the polymorphism of RYR1 C6487T by using polymerase chain reaction-restriction fragment length polymorphism and analyzed different genotypes and allelic genes to explore their associations with the risk of congenital hypospadias.…”

Section: Discussionmentioning

confidence: 99%

Genetic Polymorphism in the RYR1 C6487T Is Associated with Severity of Hypospadias in Chinese Han Children

Zhang

Jia

et al. 2018

BioMed Research International

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Objective Hypospadias is a common congenital malformation of the male external genitalia. Most cases have an unknown etiology, which is probably a mix of monogenic and multifactorial forms, implicating both genetic and environmental factors. Ryanodine receptor 1 (RYR1) mutations are a common cause of congenital diseases associated with both dominant and recessive inheritance in humans. Herein, we evaluated the correlations of RYR1 C6487T polymorphism with the risk and severity of hypospadias. Methods 263 congenital hypospadias children and 312 healthy children were recruited. The polymorphism of RYR1 C6487T in the peripheral blood was detected by polymerase chain reaction-restriction fragment length polymorphism, and different genotypes and allelic genes were analyzed to explore their associations with the risk of congenital hypospadias. Results The distribution frequencies of CC/CT/TT genotypes and two alleles (C and T) at RYR1 C6487T showed significant differences between the case and control groups (P < 0.05). The frequency of C allele in the case and control groups was 46.95% and 54.94%, respectively, and of T allele was 53.05% and 45.06% (P < 0.05). In addition, the distribution frequency of CC/CT/TT genotypes exhibited significant difference between patients with mild hypospadias and those with moderate or severe hypospadias (all P > 0.05), suggesting that RYR1 C6487T polymorphism is correlated with the severity of congenital hypospadias (X2 = 13.722, P = 0.001). Conclusion Our study demonstrated that RYR1 C6487T polymorphism might be associated with an increased risk of congenital hypospadias in Chinese Han children. Our findings highlight the heterogeneous nature of hypospadias genetic susceptibility.

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Section: Discussionmentioning

confidence: 99%

Genetic Polymorphism in the RYR1 C6487T Is Associated with Severity of Hypospadias in Chinese Han Children

Zhang

Jia

et al. 2018

BioMed Research International

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“…[13][14][15][16][17] Hence, the collection of statistical data on all the potential genetic and environmental causal factors is crucial for gaining a better understanding of the epidemiology and pathophysiology of hypospadias and, ultimately, for guiding public health measures capable of mitigating exogenous risk factors to the greatest extent possible. [18,19] Given that many environmental factors are ubiquitous and not easily measurable, strong evidence for a causal role in a congenital anomaly is still difficult to produce. To date, various methodologies have been used to gather scientific evidence.…”

Section: Introductionmentioning

confidence: 99%

Spatial analysis of hypospadias cases in northern France: Taking clinical data into account.

Prevost

Génin

OCCELLI

et al. 2020

Preprint

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Background Strong evidence for a causal role of environmental factors in a congenital anomaly is still difficult to produce. The collection of statistical data is crucial for gaining a better understanding of the epidemiology and pathophysiology of these anomalies. We aimed to evaluate spatial variations in hypospadias in our region, taking into account of clinical data, and evaluate association to socio-economic and ecological data. Methods All boys with hypospadias born in northern France and seen in Lille University Medical Center (Lille, France) between 1999 and 2012 were included in the analysis. We retrospectively collected geographic data, clinical data (especially known confounding factors associated with an elevated risk of hypospadias), and demographic, socio-economic and ecological data. We analyzed the whole study population and then the subset of boys lacking confounding factors. Results The study sample of 975 cases of hypospadias was characterized by significant spatial heterogeneity (p<0.005) and autocorrelation (p<0.001). We detected two high-incidence clusters that differed with regard to their land use. After the exclusion of 221 patients with confounding factors, two high-incidence clusters with significant disease risks (1.65 and 1.75, respectively; p<0.001) and a significant difference in land use (p<0.001) again appeared. The first cluster contained a higher median [interquartile range] proportion of artificialized land (0.40 [0.22;0.47]) than the remaining “neutral areas” (0.19 [0.08;0.53]) did (p<0.001). Conversely, the second cluster contained a higher median proportion of rural land (0.90 [0.78;0.96]) than the “neutral areas” (0.81 [0.47;0.92]) did (p<0.001). The median deprivation index was significantly lower in the urban cluster (0.47 [0.42;0.55]) and significantly higher in the rural cluster (0.69 [0.56;0.73]) (p<0.001). Conclusions Our results evidenced the heterogeneous spatial distribution of cases of hypospadias in northern France. We identified two clusters with different environmental and social patterns – even after the exclusion of known confounding factors.

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“…The suspected causal factors include genetic factors, [4][5][6][7] iatrogenic factors (e.g. medications taken during pregnancy [8][9][10] or conception via assisted reproductive technologies (ART) [11,12]) and environmental factors (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…fetal exposure to endocrine-disrupting chemicals or other chemical hazards) [13][14][15][16][17]. Hence, the collection of statistical data on all the potential genetic and environmental causal factors is crucial for gaining a better understanding of the epidemiology and pathophysiology of hypospadias and, ultimately, for guiding public health measures capable of mitigating exogenous risk factors to the greatest extent possible [5,18]. Given that many environmental factors are ubiquitous and not easily measurable, strong evidence for a causal role in a congenital anomaly is still difficult to produce.…”

Section: Introductionmentioning

confidence: 99%

Spatial analysis of hypospadias cases in northern France: taking clinical data into account

Prevost¹,

Génin²,

Occelli

et al. 2020

BMC Pediatr

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Background Strong evidence for a causal role of environmental factors in a congenital anomaly is still difficult to produce. The collection of statistical data is crucial for gaining a better understanding of the epidemiology and pathophysiology of these anomalies. We aimed to evaluate spatial variations in hypospadias within our region and it’s association to socioeconomic and ecological factors, taking clinical data into account. Methods All boys with hypospadias born in northern France and seen in Lille University Medical Center (Lille, France) between 1999 and 2012 were included in the analysis. We retrospectively collected geographic data, clinical data (especially known confounding factors associated with an elevated risk of hypospadias), and demographic, socio-economic and ecological data. We analyzed the entire study population and subsequently the subset of boys lacking confounding factors. Results The study sample of 975 cases of hypospadias over the 13-year period resulted in an incidence of 25.4/10,000 male births, and was characterized by significant spatial heterogeneity (p < 0.005) and autocorrelation (p < 0.001). We detected two high-incidence clusters that differed with regard to their land use. After the exclusion of 221 patients with confounding factors, two high-incidence clusters with significant disease risks (1.65 and 1.75, respectively; p < 0.001) and a significant difference in land use (p < 0.001) again appeared. The first cluster contained a higher median [interquartile range] proportion of artificialized land (0.40 [0.22;0.47]) than the remaining “neutral areas” (0.19 [0.08;0.53]) did (p < 0.001). Conversely, the second cluster contained a higher median proportion of rural land (0.90 [0.78;0.96]) than the “neutral areas” (0.81 [0.47;0.92]) did (p < 0.001). The median deprivation index was significantly lower in the urban cluster (0.47 [0.42;0.55]) and significantly higher in the rural cluster (0.69 [0.56;0.73]) (p < 0.001). Conclusions Our results evidenced the heterogeneous spatial distribution of cases of hypospadias in northern France. We identified two clusters with different environmental and social patterns – even after the exclusion of known confounding factors.

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Genetic and environmental factors in the aetiology of hypospadias

Cited by 22 publications

References 99 publications

Genetic Polymorphism in the RYR1 C6487T Is Associated with Severity of Hypospadias in Chinese Han Children

Genetic Polymorphism in the RYR1 C6487T Is Associated with Severity of Hypospadias in Chinese Han Children

Spatial analysis of hypospadias cases in northern France: Taking clinical data into account.

Spatial analysis of hypospadias cases in northern France: taking clinical data into account

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