Mild CFTR mutations and genetic predisposition to lactase persistence in cystic fibrosis

Abstract

Taking into account the reported incidence of hypolactasia in cystic fibrosis (CF) and the possible impact of milk products on nutritional status we aimed to assess the genetic predisposition to adult-type hypolactasia (ATH) and its incidence in CF. Single nucleotide polymorphism upstream of the lactase gene (LCT) was assessed in 289 CF patients. In subject with À13910C/C genotype (C/C) predisposing to ATH, hydrogen-methane breath test (BT) with lactose loading was conducted and clinical symptoms typical for lactose malabsorption were assessed. The percentage of CF patients with C/C was similar to that observed in healthy subjects (HS) (31.5 vs 32.5% ). Eleven out of 52 (24.5%) CF C/C patients had abnormal BT results. The recalculated frequency of lactose malabsorption was similar for the entire CF and HS populations (6.9 vs 7.2%). Similarly as in the control group, few CF patients have identified and linked to lactose consumption clinical symptoms. The frequency of LCT polymorphic variants in CF patients having and not having severe mutations of CFTR gene showed significant differences. The C allele was more frequent in homozygotes of the severe mutations than in patients carrying at least one mild/unknown mutation (Po0.0028) and in patients with at least one mild mutation (Po0.0377). In conclusion, CF patients carrying mild CFTR mutations seem to have lower genetic predisposition to ATH. Lactose malabsorption due to ATH in CF is not more frequent than in the general population. Symptomatic assessment of lactose malabsorption in CF is not reliable.

Lactose malabsorption is a risk factor for decreased bone mineral density in pancreatic insufficient cystic fibrosis patients

“…The following mutations on alleles were found (n): F508del (132), CFTR dele2,3(21kB) (12), N1303K (6), 1717-1G-A (6), R533X (4), G542X (3), 2143delT (2), W1282X (2), 2184insA (2), G551D (1), 622GA (1), LT2143 (1), unknown mutations (18). A total of 56 patients were F508del homozygous and 20 were F508del heterozygous.…”

“…The details of the applied methodologies concerning genetic testing and hydrogen-methane breath testing are described elsewhere. 18,19 BMD was assessed in the lumbar spine (L2-4) with the use of dual-emission X-ray absorptiometry, bone densitometer Lunar DPX-IQ; version 4.7e ( Madison, WI, USA). A BMD value of o À1 was assumed to be abnormal.…”

“…However, lactose malabsorption (LM), as a clinical manifestation of ATH in young people, is significantly less frequent in healthy subjects and CF patients. 18 Taking into account the expected pivotal dietary role of milk products in CF subjects, the aim of the study is to assess the potential influence of ATH and LM on BMD in adolescent and young adult patients.…”

Lactose intolerance: genetics of lactase polymorphisms, diagnosis and novel therapy

“…In addition to being a major cause of inconvenience in itself, lactose intolerance could be associated with other health disorders like cystic fibrosis, an autosomal recessive disorder characterized by the loss of function of the cystic fibrosis transmembrane conductance regulator (CFTR) (71,72). This occurs due to more than 1700 different mutations in the CFTR gene, the most common of which is the loss of phenylalanine at the 508 position of the CFTR protein resulting in its misfolding, a faulty posttranslational processing and endoplasmic reticulum regulated degradation (73).…”

Adult Lactose Digestion Status and Effects on Disease

“…The cystic fibrosis sodium transport receptor may also have evolved in Europe (124)(125)(126). It is postulated that the heterozygous mutation of this polymorphism may have protected against diarrhea caused by agents incurred by milk drinking.…”