{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:27:08Z","timestamp":1787840828737,"version":"build-2784847793"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>\n                    A\n                    <jats:sc>BSTRACT<\/jats:sc>\n                  <\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Disorders of sex development (DSD) and isolated hypospadias are congenital conditions characterized by atypical male genital differentiation, often linked to impaired androgen biosynthesis or signaling. The steroid 5\u03b1-reductase type 2 (SRD5A2) gene, encoding SRD5A2, is crucial for dihydrotestosterone biosynthesis, and its V89L polymorphism has been investigated as a potential risk factor for DSD. However, the results across the studies have been inconsistent. This synthesis was conducted to assess the association between the\n                      <jats:italic toggle=\"yes\">SRD5A2<\/jats:italic>\n                      V89L polymorphism and the risk of 46, XY DSD and isolated hypospadias through a systematic review and meta-analysis, clarifying its inheritance pattern and clinical significance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>PubMed, Scopus, and Google Scholar were queried systematically for relevant studies. Meta-analysis was performed under five genetic models: allelic (V vs. L), dominant (LL + VL vs. VV), recessive (LL vs. VL + VV), codominant (LL vs. VV and VL vs. VV), and overdominant (VL vs. LL + VV). Pooled odds ratios (OR) with 95% confidence intervals (CIs) were calculated using a random effects model. Publication bias and heterogeneity were assessed through funnel plots, Begg\u2019s test, and sensitivity analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Nine case-control studies comprising 1232 cases and 1616 controls were included. Significant associations were found in the allelic (OR = 2.05, 95% CI: 1.28\u20133.28,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.003), dominant (OR = 2.14, 95% CI: 1.23\u20133.73,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.007), and recessive models (OR = 2.46, 95% CI: 1.29\u20134.67,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.006). The codominant model analysis demonstrated a dose-dependent gene effect, where heterozygous VL carriers had a moderate risk (OR = 1.66, 95% CI: 1.01\u20132.72,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.04) while homozygous LL carriers exhibited the highest risk (OR = 3.38, 95% CI: 1.51\u20137.56,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.003) compared to VV carriers. The overdominant model showed no significant association (OR = 1.10, 95% CI: 0.80\u20131.51,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.57). The robustness of the findings was demonstrated through sensitivity analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      This meta-analysis provides strong evidence for a codominant inheritance pattern of the\n                      <jats:italic toggle=\"yes\">SRD5A2<\/jats:italic>\n                      V89L polymorphism with a stepwise increase in the risk of DSD per L allele. The results support the role of V89L as a genetic susceptibility factor in 46, XY DSD and isolated hypospadias. The findings have clinical implications for genetic counseling, early diagnosis, and potential therapeutic targeting.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/jiaps.jiaps_302_25","type":"journal-article","created":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T04:00:23Z","timestamp":1774065623000},"page":"334-345","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Gene-Dosage Effect of V89L Variants in Steroid 5\u03b1-Reductase Type 2 and Increased Risk of 46, XY Disorders of Sex Development: A Systematic Review and Meta-Analysis"],"prefix":"10.4103","volume":"31","author":[{"given":"Farah","family":"Deeba","sequence":"first","affiliation":[{"name":"Department of Paediatric Surgery, All India Institute of Medical Sciences, New Delhi, 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