Table 4.

Genetic associations tested between SLC6A14 variants and digestive and pulmonary manifestations in CF patients

rs ID (Alleles)	MAF	Variant localization	Association with	Number of CF patients	Cohort/patients characteristics	Ref
rs7879546 (T/C)	0.41	Intergenic	Lung disease severity	6365	Mean age: 19.5 years; PI (99.8%); F508del homozygotes (65%)	[8]
rs5905376 (C/A)	0.23	Intergenic	Lung disease severity
rs5952223 (C/T)	0.23	Intergenic	Lung disease severity
rs12839137 (G/A)	0.12	Intergenic	Presence of meconium ileus	6135	Two independent cohorts (patients with two severe CFTR mutations): 3,763 North American (F508del homozygotes 71.4%) and 2,372 French (> 6 years old) and American patients	[14]
			No association with pediatric lung disease severity	815	Mean age of lung function measurements: 12.63 years; F508del homozygotes: 62.3%	[10]
			No association with age of first infection by P. aeruginosa	730	Median age at first detection of positive P. aeruginosa culture: 5.55 years; F508del homozygotes: 61%
			No association with early exocrine pancreatic disease	126	Median age of the first available IRT measurement: 0.36 years; F508del homozygotes: 60.3%
			No association with early exocrine pancreatic damage	111	Patients from Colorado, median age at IRT measurement: 2 days; F508del homozygotes: 56%	[11]
rs5905283 (A/C)	0.47	Intergenic (2 KB Upstream Variant)	Presence of meconium ileus	6,135	Two independent cohorts (patients with two severe CFTR mutations): 3,763 North American (F508del homozygotes 71.4%) and 2,372 French (> 6 years old) and American patients	[14]
			Pediatric lung disease severity	815	Mean age of lung function measurements: 12.63 years; F508del homozygotes: 62.3%	[10]
			No association with age of first infection by P. aeruginosa	730	Median age at first detection of positive P. aeruginosa culture: 5.55 years; F508del homozygotes: 61%
			No association with early exocrine pancreatic phenotypes	126	Median age of the first available IRT measurement: 0.36 years; F508del homozygotes: 60.3%
			No association with early exocrine pancreatic damage	111	Patients from Colorado, median age at IRT measurement: 2 days; F508del homozygotes: 56%	[11]
rs3788766 (G/A)	0.36	Regulatory region	Presence of meconium ileus	6,135	Two independent cohorts (patients with two severe CFTR mutations): 3,763 North American (F508del homozygotes 71.4%) and 2,372 French (> 6 years old) and American patients	[14]
			Pediatric lung disease severity	815	Mean age of lung function measurements: 12.63 years; F508del homozygotes: 62.3%	[10]
			Age of first infection by P. aeruginosa	730	Median age at first detection of positive P. aeruginosa culture: 5.55 years; F508del homozygotes: 61%
			No association with early exocrine pancreatic phenotypes	126	Median age of the first available IRT measurement: 0.36 years; F508del homozygotes: 60.3%
			No association with early exocrine pancreatic damage	111	Patients from Colorado, median age at IRT measurement: 2 days; F508del homozygotes: 56%	[11]
			Early pulmonary symptoms	79	Brazilian patients	[12]
			P. aeruginosa infection	83
			Presence of meconium ileus	6,770	Patients with two severe CFTR mutations associated with PI; F508del homozygotes: 64.2%	[9]
rs12710568 (G/C)	0.31	Regulatory region	Presence of meconium ileus	6,770	Patients with two severe CFTR mutations associated with PI; F508del homozygotes: 64.2%	[9]
rs5905177 (C/T)	0.35	SLC6A14 intron	Presence of meconium ileus

Chromosomic position (forward strand); minor allele in the European population, Minor allele Frequency (MAF), data were collected from Ensembl, 1000 Genomes, European population. IRT immunoreactive trypsinogen, PI pancreatic insufficiency