Gene-gene interaction between serotonin transporter

SILVIA SOOKOIAN; TOMAS FERNANDEZ GIANOTTI; ADRIANA BURGUEÑO; CARLOS JOSE PIROLA

CHRONOBIOLOGY INTERNATIONAL

TAYLOR & FRANCIS INC

Año: 2010 vol. 6 p. 1202 - 1218

0742-0528

Serotonergic neurotransmission and the master circadian CLOCK gene are physiological modulators of the circadian system. In addition, both are involved in the physiopathology of metabolic syndrome (MS). The authors sought to examine the potential effect of the gene-gene interaction between the functional 44-bp insertion/deletion polymorphism in the promoter region (serotonin-transporter-linked promoter region polymorphism or 5-HTTLPR) of the serotonin transporter gene (SLC6A4) and common variants of the gene CLOCK on the genetic risk underlying MS of shiftworkers. To test this hypothesis, 856 men were studied; 518 dayworkers were compared with 338 rotating shiftworkers. Medical history, health examination including anthropometric and arterial blood pressure measurements, a questionnaire on health-related behaviors, and biochemical determinations were obtained from every participant. 5-HTTLPR genotypes were determined using polymerase chain reaction followed by gel electrophoresis. Six tag single-nucleotide polymorphisms (SNPs) in the CLOCK gene with a minor allele frequency >10 % (rs1554483 C/G, rs11932595 A/G, rs4580704 C/G, rs6843722 A/C, rs6850524 C/G, and rs4864548 A/G), encompassing 117 kb of chromosome 4 and representing 115 polymorphic sites (r2 > .8), were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= 117 kb of chromosome 4 and representing 115 polymorphic sites (r2 > .8), were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= A/G, rs4580704 C/G, rs6843722 A/C, rs6850524 C/G, and rs4864548 A/G), encompassing 117 kb of chromosome 4 and representing 115 polymorphic sites (r2 > .8), were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= 117 kb of chromosome 4 and representing 115 polymorphic sites (r2 > .8), were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= To test this hypothesis, 856 men were studied; 518 dayworkers were compared with 338 rotating shiftworkers. Medical history, health examination including anthropometric and arterial blood pressure measurements, a questionnaire on health-related behaviors, and biochemical determinations were obtained from every participant. 5-HTTLPR genotypes were determined using polymerase chain reaction followed by gel electrophoresis. Six tag single-nucleotide polymorphisms (SNPs) in the CLOCK gene with a minor allele frequency >10 % (rs1554483 C/G, rs11932595 A/G, rs4580704 C/G, rs6843722 A/C, rs6850524 C/G, and rs4864548 A/G), encompassing 117 kb of chromosome 4 and representing 115 polymorphic sites (r2 > .8), were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= 117 kb of chromosome 4 and representing 115 polymorphic sites (r2 > .8), were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= A/G, rs4580704 C/G, rs6843722 A/C, rs6850524 C/G, and rs4864548 A/G), encompassing 117 kb of chromosome 4 and representing 115 polymorphic sites (r2 > .8), were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= 117 kb of chromosome 4 and representing 115 polymorphic sites (r2 > .8), were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= common variants of the gene CLOCK on the genetic risk underlying MS of shiftworkers. To test this hypothesis, 856 men were studied; 518 dayworkers were compared with 338 rotating shiftworkers. Medical history, health examination including anthropometric and arterial blood pressure measurements, a questionnaire on health-related behaviors, and biochemical determinations were obtained from every participant. 5-HTTLPR genotypes were determined using polymerase chain reaction followed by gel electrophoresis. Six tag single-nucleotide polymorphisms (SNPs) in the CLOCK gene with a minor allele frequency >10 % (rs1554483 C/G, rs11932595 A/G, rs4580704 C/G, rs6843722 A/C, rs6850524 C/G, and rs4864548 A/G), encompassing 117 kb of chromosome 4 and representing 115 polymorphic sites (r2 > .8), were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= 117 kb of chromosome 4 and representing 115 polymorphic sites (r2 > .8), were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= A/G, rs4580704 C/G, rs6843722 A/C, rs6850524 C/G, and rs4864548 A/G), encompassing 117 kb of chromosome 4 and representing 115 polymorphic sites (r2 > .8), were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= 117 kb of chromosome 4 and representing 115 polymorphic sites (r2 > .8), were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p= To test this hypothesis, 856 men were studied; 518 dayworkers were compared with 338 rotating shiftworkers. Medical history, health examination including anthropometric and arterial blood pressure measurements, a questionnaire on health-related behaviors, and biochemical determinations were obtained from every participant. 5-HTTLPR genotypes were determined using polymerase chain reaction followed by gel electrophoresis. Six tag single-nucleotide polymorphisms (SNPs) in the CLOCK gene with a minor allele frequency >10 % (rs1554483 C/G, rs11932595 A/G, rs4580704 C/G, rs6843722 A/C, rs6850524 C/G, and rs4864548 A/G), encompassing 117 kb of chromosome 4 and representing 115 polymorphic sites (r2 > .8), were genotyped. A significant interaction between the 5-HTTLPR variant and the haplotype rs1554483–rs4864548 of the CLOCK gene was detected for diastolic ( p