IRF6 rs2235375 single nucleotide polymorphism is associated with isolated non-syndromic cleft palate but not with cleft lip with or without palate in South Indian population / Polimorfismo de nucleotídeo único do gene IRF6 rs2235375 está associado com à fenda palatina isolada não sindrômica, mas não com fenda labial com ou sem fenda palatina em população do sul da Índia

Abstract Introduction Transcription factors are very diverse family of proteins involved in activating or repressing the transcription of a gene at a given time. Several studies using animal models demonstrated the role of transcription factor genes in craniofacial development. Objective We aimed to investigate the association of IRF6 intron-6 polymorphism in the non-syndromic cleft lip with or without palate in a South Indian population. Methods 173 unrelated nonsyndromic cleft lip with or without cleft palate patients and 176 controls without clefts patients were genotyped for IRF6 rs2235375 variant by allele-specific amplification using the KASPar single nucleotide polymorphism genotyping system. The association between interferon regulatory factor-6 gene intron-6 dbSNP208032210:g.G>C (rs2235375) single nucleotide polymorphism and non-syndromic cleft lip with or without palate risk was investigated by chi-square test. Results There were significant differences in genotype or allele frequencies of rs2235375 single nucleotide polymorphism between controls and cases with non-syndromic cleft lip with or without palate. IRF6 rs2235375 variant was significantly associated with increased risk of non-syndromic cleft lip with or without palate in co-dominant, dominant (OR: 1.19; 95% CI 1.03-2.51; p = 0.034) and allelic models (OR: 1.40; 95% CI 1.04-1.90; p = 0.028). When subset analysis was applied significantly increased risk was observed in cleft palate only group (OR dominant: 4.33; 95% CI 1.44-12.97; p = 0.005). Conclusion These results suggest that IRF6 rs2235375 SNP play a major role in the pathogenesis and risk of developing non-syndromic cleft lip with or without palate.

Resumo Introdução Fatores de transcrição constituem uma família de proteínas muito diversa envolvida na ativação ou repressão da transcrição de um gene, em um determinado momento. Vários estudos usando modelos animais demonstraram o papel dos genes do fator de transcrição no desenvolvimento craniofacial. Objetivo Nosso objetivo foi investigar a associação do polimorfismo IRF6 intron-6 na fenda labial não sindrômica com ou sem fenda palatina em uma população do sul da Índia. Método Um total de 173 pacientes com fenda labial não sindrômica com ou sem fenda palatina e 176 controles sem fendas foram genotipados para a variante IRF6 rs2235375 por amplificação alelo-específica utilizando o sistema KASPar de genotipagem de polimorfismo de nucleotídeo único. A associação entre o polimorfismo de nucleotídeo único Fator 6 Regulatório do Interferon (IRF6) intron-6 dbSNP208032210:g.G>C (rs2235375) e o risco de fenda labial não sindrômica com ou sem fenda palatina foi investigado pelo teste qui-quadrado. Resultados Houve diferenças significativas nas frequências de genótipos ou alelos do rs2235375 SNP entre controles e casos com fenda labial não sindrômica com ou sem fenda palatina. A variante IRF6 rs2235375 foi significativamente associada ao aumento do risco de fenda labial não sindrômica com ou sem fenda palatina em modelos codominantes, dominantes (OR: 1,19; IC 95%: 1,03-2,51; p = 0,034) e alélicos (OR: 1,40; IC 95%: 1,04-1,90; p = 0,028). Quando a análise do subgrupo foi realizada, um risco significativamente aumentado foi observado no grupo Fenda Palatina Isolada (OR dominante: 4,33; IC 95%: 1,44-12,97; p = 0,005). Conclusões Esses resultados sugerem que o polimorfismo de nucleotídeo único IRF6 rs2235375 desempenha um papel importante na patogênese e no risco de desenvolvimento de fenda labial não sindrômica com ou sem fenda palatina.

Influence of angiotensin converting enzyme (ACE) gene rs4362 polymorphism on the progression of kidney failure in patients with autosomal dominant polycystic kidney disease (ADPKD).

Background & objectives: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, characterized by the fluid filled cysts in the kidneys leading to end stage renal failure in later years of life. Hypertension is one of the major factors independently contributing to the chronic kidney disease (CKD) progression. The renin-angiotensin aldosterone system (RAAS) genes have been extensively studied as hypertension candidate genes. The aim of the present study was to investigate the role of angiotensin converting enzyme tagging - single nucleotide polymorphisms (ACE tag-SNPs) in progression of CKD in patients with ADPKD. Methods: In the present study six ACE tagSNPs (angiotensin converting enzyme tag single nucleotide polymorphisms) and insertion/deletion (I/D) in 102 ADPKD patients and 106 control subjects were investigated. The tagSNPs were genotyped using FRET-based KASPar method and ACE ID by polymerase chain reaction (PCR) and electrophoresis. Genotypes and haplotypes were compared between ADPKD patients and controls. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on CKD advancement. Mantel-Haenszel (M-H) stratified analysis was performed to study the relationship between different CKD stages and hypertension and their interaction. Results: All loci were polymorphic and except rs4293 SNP the remaining loci followed Hardy-Weinberg equilibrium. Distribution of ACE genotypes and haplotypes in controls and ADPKD patients was not significant. A significant linkage disequilibrium (LD) was observed between SNPs forming two LD blocks. The univariate analysis revealed that the age, hypertension, family history of diabetes and ACE rs4362 contributed to the advancement of CKD. Interpretation & conclusions: The results suggest that the ACE genotypes are effect modifiers of the relationship between hypertension and CKD advancement among the ADPKD patients.