title: Single nucleotide polymorphisms of the tenomodulin gene (TNMD) in age-related macular degeneration.
abstract: OBJECTIVE
  Tenomodulin (TNMD) is located in the X-chromosome encoding a putative angiogenesis inhibitor which is expressed in retina. Associations of single nucleotide polymorphisms of TNMD with the prevalence of age-related macular degeneration (AMD) were examined.
  
  
  METHODS
  Six markers covering 75% of the common sequence variation in the coding region of TNMD and 10 kb up- and downstream were genotyped in a sample consisting of 89 men and 175 women with exudative AMD, 18 men and 25 women with atrophic AMD, and 55 men and 113 women without AMD. All participants were over 65 years old and did not have diabetes mellitus. Due to the chromosomal locus, the association of genotypes with AMD was assessed genderwise.
  
  
  RESULTS
  Three markers, rs1155974, rs2073163, and rs7890586, were associated with a risk of AMD in women. In comparison to women with other genotypes, the women who were homozygous for the minor allele (genotypes rs1155974-TT or rs2073163-CC) had 2.6 fold (p=0.021) or 1.9 fold (p=0.067) risk for having AMD, respectively. These differences were due to the unequal prevalence of exudative AMD. In comparison to women who were homozygous for the major alleles, the women with rs1155974-TT genotype had a 2.8 fold risk (p=0.021 in additive model; p=0.022 in recessive model) for exudative AMD, and the women with rs2073163-CC genotype had a 1.8 fold risk (p=0.09 in additive model; p=0.038 in recessive model). Furthermore, women carrying the rare rs7890586-AA genotype had a significantly smaller risk for having AMD than women with the other genotypes (odds ratio 0.083; p=0.001 in recessive model), but due to the low frequency of this genotype, this finding must be interpreted cautiously. The false discovery rate was <10% for all of the aforementioned results.
  
  
  CONCLUSIONS
  On the basis of the putative antiangiogenic role of TNMD and the present genetic associations of TNMD with AMD in women, we suggest that TNMD could be a novel candidate gene for AMD. These results should be confirmed in further studies.
authors.affiliation: Department of Clinical Nutrition and Food and Health Research Centre, University of Kuopio, Kuopio, Finland. anna-maija.tolppanen@uku.fi
authors.forename: Anna-Maija
authors.initials: AM
authors.lastname: Tolppanen
authors.forename: Tanja
authors.initials: T
authors.lastname: Nevalainen
authors.forename: Marjukka
authors.initials: M
authors.lastname: Kolehmainen
authors.forename: Sanna
authors.initials: S
authors.lastname: Seitsonen
authors.forename: Ilkka
authors.initials: I
authors.lastname: Immonen
authors.forename: Matti
authors.initials: M
authors.lastname: Uusitupa
authors.forename: Kai
authors.initials: K
authors.lastname: Kaarniranta
authors.forename: Leena
authors.initials: L
authors.lastname: Pulkkinen
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D008565:Membrane Proteins; C422444:TNMD protein, human